Genetic regulation of the organism at different stages of ontogenesis. The concept of ontogenesis

Ontogenesis- the process of individual development of an organism (from its birth to death). The period of ontogenesis from fertilization of the egg to the release of the young individual from the egg shells or the mother’s body is called germinal, or embryonic, development (embryogenesis); After birth, the postembryonic period begins.

The study of heredity and variability has shown that the sequential development of the characteristics of an organism in ontogenesis occurs under the control of the genetic apparatus. At different stages of ontogenesis, coordinated regulation of the activity of various genes occurs. The mechanisms of this regulation and the specific sequence of deployment of the genetic program in the ontogenesis of various species of organisms are being intensively studied. It has been proven that although all cells of one organism potentially carry the same genetic program, but, firstly, as the organism develops, its different cells use different parts of this program, and secondly, the nature of the work of genes is greatly influenced by external conditions , in relation to the cell and to the given organism, environment.

Main stages of ontogenesis.

Types of ontogeny.

  1. Direct (no transformation)
    1. Non-larval (oviparous)

eggs are rich in nutrients, a significant part of ontogenesis in the egg in the external environment

    1. Intrauterine

provision of vital functions and development of the embryo by the maternal body through the placenta, the role of provisional organs

  1. Indirect (with transformation)
    1. Complete: egg – larva – pupa – adult
    2. Not complete: egg – larva – adult

Periodization of ontogeny

  1. General biological(according to the individual’s ability to perform the reproductive function)
    1. Progenesis
    2. Pre-reproductive
      1. Embryonic

Development inside egg membranes

The embryo is relatively isolated from environment

The shortest in Placentals - several days before implantation of the blastocyst into the uterus

Longest in birds and other oviparous species

The release of the blastocyst from the shell is the end of the embryonic period in Platsntarnye

      1. Larval

May last from days or months to several years (lamreys)

The larva is a free-living embryo. It has temporary (provisional) organs

The period is important for nutrition and settlement

In humans, the larval period is homologous to the period of fetal development in the uterus

Some species reach sexual maturity at the larval stage (Axolotl is an amblyoma larva, capable of reproducing)

      1. Metamorphosis (transformation)

The larva turns into a juvenile (young) form

Larval (provisional) organs disappear, the body is rebuilt and organs of adult life appear

In humans, it is homologous to childbirth. When the embryonic membranes are discarded, blood circulation, respiration, hemoglobin, etc. change.

      1. Juvenile

Lasts until puberty

Rapid growth is taking place

In mammals and birds, the young are highly dependent on their parents

    1. Reproductive

Stunting of growth and active reproduction

Secondary sexual characteristics

There are species that reproduce once (salmon) and repeatedly (the larger the litter, the shorter the life expectancy of the species)

    1. Post-reproductive (aging)

Associated with aging, characterized by cessation of participation in reproduction, resistance decreases. Distinguish external signs old age (decrease in skin elasticity, graying of hair, development of farsightedness) and internal (reverse development of organs, decreased elasticity of blood vessels, impaired blood supply to the brain, heart activity, etc.). All this leads to a decrease in viability and an increase in the likelihood of death.

There are dozens of hypotheses explaining the mechanisms of aging. Currently, scientists consider 2 main causes of aging:

· wear and tear of biological structures due to age-related accumulation of errors in cellular mechanisms under the influence of mutations;

· genetically predetermined destruction.

    1. Death

Death as a biological phenomenon is a universal way to limit the participation of a multicellular organism in reproduction, to ensure a change of generations and the evolutionary process. The rate of increase and severity of changes in the aging process depends on the genotype, living conditions, lifestyle, incl. nutrition

  1. Embryological (according to ongoing processes)
    1. Crushing
    2. Gastrulation
    3. Histo- and organogenesis
  2. Anthropological
    1. Prezygotic (preembryonic)

The period of formation and maturation of germ cells

    1. Prenatal (embryonic)

It begins with the moment of fertilization and ends with birth or emergence from the egg. After fertilization, the zygote begins to fragment, the blastomeres gradually line up along the periphery, forming a single-layer embryo - the blastula. Then a two-layer embryo is formed - the gastrula, which has ectoderm and endoderm, a primary mouth - the blastopore and a cavity - the gastrocoel. At the next stage, the third layer of cells is formed - the mesoderm. Further, tissues and organs are formed from these layers of cells, i.e. histo- and organogenesis occurs.

      1. Elementary– 1 week after fertilization
      2. Embryonic(the embryo is called an embryo) – from the 2nd to the 9th week after fertilization
      3. Fetal(the embryo is called a fetus) – from the 9th to the 40th week
    1. Postnatal (postembryonic)
      1. Newborn(1-10 days). A difficult period of adaptation to completely new living conditions
      2. Chest(up to 1 year). The baby is fed with mother's milk, which contains, in addition to nutrients, salts and vitamins ready-made antibodies
      3. Early childhood(1 -3 years). The child learns to walk, speak normally, and begins to explore the world around him.
      4. First childhood(4-6 years old). The child is interested in everything around him and strives to understand it.
      5. Second childhood(m 7-12 years old, female 7-11 years old). School period before puberty
      6. Teenage(m 13-16 years old, female 12-15 years old). Period of puberty
      7. Youthful(m 17-21 years old, female 16-20 years old). The end of growth, sexual and physical maturation
      8. First maturity(m 22-35 years old, female 21-35 years old). The best period for childbearing
      9. Second maturity(m 36-60 years old, female 36-55 years old). The period of maximum professionalism; after 35 years, changes are detected in some physiological and biochemical metabolic reactions that precede involution; by the end of this period, changes occur that determine the beginning of the aging process and mechanisms are activated that ensure the restructuring of the body and its adaptation
      10. Elderly(m 61-75 years old, female 56-75 years old). During this period, many people still retain sufficient professional capacity, although the aging process continues to develop
      11. Senile(76-90 years old). Age-related changes are noticeable, but at this age many people retain clarity of mind and the ability to do creative work
      12. Centenarians(over 90 years). Mostly women survive until this last period of ontogenesis.

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Regulation of ontogeny

Introduction

Genetic regulation of organism development

Cell contact interaction

Embryonic induction

Morphogenetic fields

Old age and aging

References

Introduction

Why and how is the genotype realized into a phenotype in the form of certain cellular and systemic processes, in the form of complex spatial and temporally ordered ontogenetic transformations?

When comparing the zygote and the sexually mature individual, which, in fact, are two different ontogenetic stages of the existence of the same organism, obvious differences are revealed, regarding at least size and shape. Since the 17th century. scientists tried to understand and explain the processes leading to these quantitative and qualitative changes in the individual.

Initially, a hypothesis arose according to which ontogenesis was considered only as the growth of pre-existing structures and parts of the future organism located in a certain spatial order.

Under this hypothesis, called preformationism, no new formations or structural transformations occur in individual development. The logical conclusion of the idea of ​​preformationism lies in the assumption of the absurd idea of ​​the “preparedness” in the zygote and even in the germ cells of the ancestors of the structures of organisms of all subsequent generations, as if nested sequentially like wooden nesting dolls.

Alternative concept epigenesis was formulated in the middle of the 18th century. F.K. Wolf, who first discovered the formation of the neural tube and intestines during embryonic development. Individual development began to be associated entirely with qualitative changes, believing that structures and parts of the body arise as new formations from a structureless egg.

In the 19th century K. Baer was the first to describe the egg of mammals, including humans, as well as the germ layers and discovered the similarity of the structural plan of the embryos of various classes of vertebrates - fish, amphibians, reptiles, birds, mammals.

He also drew attention to the continuity in the stages of development - from simpler to more complex. Baer considered ontogenesis not as transformation, not like neoplasm structures, and how to transformation, which is quite consistent with modern ideas.

Developmental biology seeks to clarify the degree and specific ways of control by the genome and at the same time the level of autonomy of various processes during ontogenesis. No less important are studies of specific ontogenetic mechanisms of growth and morphogenesis. These include the following cellular mechanisms: proliferation, or cell multiplication, migration, or movement of cells, cell sorting, their programmed death, cell differentiation, contact interactions of cells (induction and competence), distant interactions of cells, tissues and organs (paracrine, humoral and neural mechanisms of integration). All these processes are selective in nature, i.e. occur within a certain space-time framework with a certain intensity, obeying the principle of the integrity of the developing organism.

Ontogenesis (from the Greek Ontos - existing and genesis - development) is the individual development of each individual. This is a complex process of formation of a living organism from birth to death. In unicellular organisms, ontogenesis begins with the division of the mother organism into daughter organisms and continues until the next division of the daughter organism. During asexual reproduction of multicellular organisms, ontogeny begins with one or a group of somatic cells from which a daughter organism is formed and ends with death.

During sexual reproduction, three periods of individual development are distinguished: genetic intercellular ontogenesis substrate

1. Preembryonic(proembryonic), or progenesis, is the period of formation of germ cells and fertilization.

2. Embryonic(embryonic) - the period that passes from the formation of the zygote until its release from the egg membranes or birth.

3. Postembryonic(postembryonic) - includes development until puberty (juvenile period), adulthood (reproductive period), postreproductive

period, aging and death of the body. In the juvenile period, development can be direct (non-larval type) or with metamorphosis (larval type).

Changes at different stages of ontogenesis occur at different rates, are most intense in embryogenesis, then gradually slow down. Especially during puberty.

At the end of the reproductive period, the natural end of ontogenesis is the death of the individual.

However, the ontogenesis of each multicellular organism is based on general mechanisms of growth and development, carried out through the processes of cell division, differentiation, and morphogenetic movement. The two main principles of ontogenesis - differentiation (specialization of its individual parts) and integration - the unification of individual parts and their subordination to a single organism, manifest themselves at all stages of ontogenesis and at all levels of the organism. Biology. Guide to practical classes: training manual. Markina V.V., Oborotistov Yu.D., Lisatova N.G. and others / Ed. V.V. Markina. 2010. -

According to modern concepts, a certain genetic development program is embedded in the somatic cell (asexual reproduction) or zygote (sexual reproduction), from which a new organism develops. In ontogenesis, this program is implemented, determining the general direction of morphogenetic processes, but specific implementation is carried out depending on environmental conditions, within the limits of the reaction norm.

Geneticregulationdevelopmentbody

Genes regulate and control the development of the organism at all stages of ontogenesis. According to modern concepts, a gene can be defined as a unit hereditary information. Occupying a certain position in the genome or chromosome and controlling the performance of a certain function in the body.

Thanks to ontogenesis, which occurs under certain environmental conditions, hereditary information is embodied in structures and processes. Based on genotype is being formed phenotype individuals of a given biological species. Since natural selection occurs in living nature according to phenotypes, it is in the development of an individual with a species-specific phenotype that the main evolutionarily significant event at the organismal or ontogenetic level lies.

If we keep in mind the material-energy and bioinformational support of the ontogenesis of an individual, then we should make a reservation that it begins before the moment of fertilization and the formation of the zygote and is associated mainly with the female reproductive cell. The latter, during gametogenesis (ovogenesis), acquires some characteristics that will be used not by itself, but by an individual of a new generation that has begun individual development. One of these characteristics, perhaps the most well-known, is the formation in the cytoplasm of the egg of a larger or smaller amount of yolk, depending on the type of animal, which is used as nutritional material during the development of the offspring. The functional and genetic activity of a number of genes, manifested in their transcription and post(post)transcriptional changes in the primary and (m)RNA transcript, is also attributed in time to the period before fertilization. The i(m)RNAs formed as a result of this activity organize the synthesis of proteins important for the early stages of embryogenesis. The totality of events occurring in ovo(oo)genesis, but in the interests of the process of individual development of a new organism, constitutes the content periodprogenesis- pre-embryonicperiodindividualdevelopment Biology: textbook: in 2 volumes / Ed. V.N. Yarygina. - M.; GEOTAR-Media, 2014. - T.1. - 736 p.: ill.

Gene expression is the process of realizing information encoded in the DNA structure at the level of RNA and proteins.

Genetic regulation controls the entire course of individual development of an organism, starting with the formation of gametes and ending with the formation of systems that regulate and coordinate the growth and vital activity of an adult organism.

During oogenesis, maternal RNAs are synthesized and deposited in the cytoplasm of the egg, which carry information about proteins and control the development of the embryo from the zygote to the blastula stage. The genes of the embryo begin to function in vertebrates at different stages of cleavage (for example, in humans at the stage of two blastomeres), and the products of their activity begin to regulate the development of the embryo. Thus, the early stages of development are regulated by maternal and germline genes. Starting from the gastrula stage, in vertebrates the development of the body is regulated only by the products of the activity of the embryo’s own genes.

Regulation of gene expression during the development of organisms is carried out at all stages of protein synthesis, both by induction and repression, and control at the transcription level determines the time of functioning of the embryo’s own genes.

In all metazoans from jellyfish to humans, embryonic differentiation along the anteroposterior axis is regulated by a group of genes called HOX. HOX proteins are transcription factors that share a homeodomain in their structure, which determines the specificity of their binding to DNA. Homeodomain - containing genes - are defined by the presence of a characteristic DNA sequence 183 base pairs long (homeobox), encoding a relatively conserved protein region 61 aa long (homeodomain). A striking feature of HOX genes is that they are expressed in the same order as they are located in the genome. The HOX genes and the proteins they encode provide a good illustration of fundamental factors about gene expression in development, such as complexity and interaction.

The XYZ gene in different parts of the embryo may be transcribed at different rates, and it may be predisposed to produce alternative transcript varieties, so that one codes for an entire family of proteins. Another group of transcription factors that are important for early development when they act as regulators of organogenesis are the PAX proteins. They are necessary to maintain the pluripotency of stem cell populations, i.e. they are capable of differentiating into many specialized cell types. The PAX1 PAX9 genes are expressed during the development of the spinal column, limb buds, and thymus, where they exhibit overlapping expression patterns. The PAXNo gene is expressed in early development in mammals, in the dorsal neural tube, the region that produces migrating neural crest cells. They are involved in the development of various organs, including the heart, peripheral and ventral ganglia, melanocytes and Schwann cells. The function of PAX6 appears to be key in the development of the eye and vision.

Contactinteractioncells

The mechanisms that ensure cell connection and intercellular information exchange were formed during the evolutionary transition from a single-celled organism to a multicellular one. Intercellular interactions are necessary to coordinate the activity, differentiation, motility and growth of cells within tissues and organs. The cells that make up the tissue are in contact not only with each other, but also with the extracellular matrix, consisting of fibers, protein, collagen and gelatin-like substances, represented by glycoproteins and proteoglycans. The extracellular matrix holds cells together and provides physical support and an environment in which they move and interact. Physiology and fundamentals of anatomy: textbook / Ed. A.V. Kotova, T.N. Loseva. 2011. - 1056 p. (Series "Educational literature for medical students")

Along with the renewal of the cell population, renewal of intracellular structures is constantly observed in the cells themselves (intracellular physiological regeneration).

Height cells manifests itself in changes in their size and shape. Cell growth is not unlimited and is determined by the optimal nuclear-cytoplasmic ratio.

Movements cells. Cell migration is most typical during the gastrulation period. Migration is carried out using several mechanisms. So, they distinguish chemotaxis- movement of cells in the direction of the concentration gradient of a chemical agent. Haptotaxis- mechanism of cell movement along a concentration gradient of an adhesion molecule. Contact orientation- when in any obstacle there is only one channel left for movement. Contact inhibition- this method of movement is observed in the tapholes of a smooth ridge.

Migration is purposeful in nature, the cells do not move chaotically, but along certain paths precisely to those parts of the embryo where mature derivatives will subsequently be formed from them. Disturbances in cell migration that occur during the period of embryogenesis lead to the formation of such congenital malformations as heterotopia and ectopia, i.e. to abnormal localization of organs or structures.

Mechanisms intercellular interactions. The formation and functioning of all tissue structures can occur only on the basis of their mutual recognition and mutual adhesion, i.e. the ability of cells to selectively attach to each other or to components of the extracellular matrix. Cell adhesion is realized by special glycoproteins - adhesion molecules - cadherin, laminin, connexin, etc. Physiology and fundamentals of anatomy: textbook / Ed. A.V. Kotova, T.N. Loseva. 2011. - 1056 p. (Series "Educational literature for medical students")

Mechanisms interactions cells With substrate. They include the formation of cell receptors for extracellular matrix molecules. The latter include cell derivatives. Among which, the most studied adhesion molecules are collagen, fibronectin, laminin, tenascin, etc.

To communicate between migrating cells and the extracellular matrix, cells form specific receptors. These include, for example, syndecan, which ensures contact of the epithelial cell with the basement membrane due to adhesion to fibronectin and collagen molecules.

Distant intercellular interactions carried out through the secretion of hormones and growth factors. The latter are substances that have a stimulating effect on the proliferation and differentiation of cells and tissues.

The influence of the position of blastomeres on their differentiation. The differentiation of a cell is influenced by its position in a certain place of the embryo in certain time. The outer cells form the trophoblast, and the inner cells form the embryo. Experience with blastomere transplantation shows that the formation of trophoblast or embryonic cells from blastomeres is determined by where the cell ends up - on the surface or inside a group of cells.

Gastrulation begins at the end of the second week of development and is characterized by the appearance of the ability of cells to move. With the onset of gastrulation, the first tissue-specific genes are activated. The embryoblast is divided into epiblast(layer of cylindrical cells) and hypoblast(layer of cubic cells facing the blastocoel). The epiblast and hypoblast together form a two-layer germinal disc (blastodisc). Subsequently, in place of the two-layer germinal disc, the primary germ layers develop through migration and proliferation of cells: ectoderm, mesoderm and endoderm. Hypoblast. The formation of the hypoblast (primary endoderm) occurs along a caudal-cranial gradient. The cells of the ventral part of the inner cell mass facing the blastocoel are separated into a thin layer - the hypoblast. Hypoblast cells are evicted from the inner cell mass due to weak adhesive interaction between them. Intensely proliferating hypoblast cells move along inner surface trophoblast and form the extraembryonic endoderm of the yolk sac wall adjacent to the trophoblast. Histology, embryology, cytology: a textbook for universities / Ed. E.G. Ulumbekova, Yu.A. Chelysheva - 3rd ed., - M.: GEOTAR-Media, 2012.

Movementscellsatgastrulation

Histology, embryology, cytology: a textbook for universities / Ed. E.G. Ulumbekova, Yu.A. Chelysheva - 3rd ed., - M.: GEOTAR-Media, 2012.

Embryonicinduction

Embryonicinduction- interaction of parts of the developing embryo, in which one part of the embryo influences the fate of another part.

Embryonicinduction or mechanisms of differentiation were discovered 1901 G. when studying the formation of the rudiment of the eye lens in amphibian embryos.

Hypothesis: There are certain cells that act as organizers of others that are suitable for that cell. In the absence of organizer cells, such cells will take a different development path, different from the one in which they would develop in the presence of organizers.

Experiment: G. Spemann and his collaborator H. Mangold discovered an “organizer” in amphibian embryos. A control experiment was carried out by Hilda Mangold in 1921. She cut a piece of tissue from the dorsal lip of the gastrula blastopore of a crested newt with a weakly pigmented embryo. She transplanted it into the ventral part of another gastrula of a closely related species, the common newt, the embryo of which is characterized by abundant pigmentation. After transplantation, a new notochord and myotomes developed from the recipient gastrula from the transplant tissue.

Several conclusions follow from this and similar experiments. Firstly, a section taken from the dorsal lip of a blastopore is capable of directing or even switching the development of the material that is around it to a certain developmental path. It sort of organizes the development of the embryo in both usual and atypical places. Secondly, the lateral and ventral sides of the gastrula have wider potential for development than their presumptive direction, since instead of normal surface body under experimental conditions, a whole embryo is formed there. Thirdly, the fairly accurate structure of the newly formed organs at the transplant site indicates embryonic regulation. This means that the factor of the integrity of the body leads to the achievement of a good final result from atypical cells in an atypical place, as if controlling the process. By adjusting it to achieve this result.

Morphogeneticfields

Morphogenesis- the process of formation of structures and organs and transformation of their shape in the process of individual development of organisms. This is undoubtedly the most complex and orderly natural process.

In classical embryology, morphogenesis is usually understood as the emergence of multicellular structures. In chordates, the first visible morphogenetic events - the formation of axial organs - are noted during neurulation. However, it should be remembered that inductive interactions of groups of cells (buds), which determine the initial stages of morphogenesis, are carried out at the blastula and early gastrula stages (see section 8.2.8). Thus, it is legitimate to believe that morphogenesis at the supracellular level begins from the blastula stage. During the period of gastrulation, as well as during neurulation, changes cover the entire embryo. The subsequent organogenesis represents increasingly local processes. Further sequential differentiation occurs within the rudiment of each of the developing organs.

In parallel with the formation of multicellular structures, subcellular and cellular elements are formed. Complex cytodifferentiation occurs, which is carried out through the coordinated activity of many intracellular formations - the membrane, microtubules and centers of their organization, the Golgi apparatus and a number of others. Thus, the differentiation of absorptive cells of the epithelium of the kidneys and intestines is associated with the assembly of powerful bundles of actin microfilaments that form the structural basis of microvilli, the size and structure of which are characterized by high accuracy (certainty). In addition, there is a restructuring cell membranes, which determines their future functional properties. These processes, in turn, are accompanied by the synthesis and spatial organization of macromolecules, in particular, the formation and integration into the plasmalemma of protein complexes that provide various types of transport of substances. Thus, morphogenesis is a multi-level dynamic process that ultimately leads to the formation of an integrated, balanced (whole) individual of a particular biological species.

Morphogenesis as growth and cell differentiation refers to acyclic processes, i.e. not returning to its previous state and for the most part irreversible. The main property of acyclic processes is their spatiotemporal organization. The problem of forming the spatial structure of a developing organism is one of the most complex in biology.

The system of genes that regulate the formation of an organ or the implementation of a specific morphogenetic process is organized according to hierarchicalprinciple. Thus, during ontogenesis, sequential activation of certain groups of genes occurs, and the products of previously activated genes affect the expression of the following groups. In gene cascades there are " genes- gentlemen" (" master- genes" ), activation of which initiates the process and includes the expression of a whole complex of subordinate “slave genes”, which ultimately leads to the formation of a certain structure.

Biology: textbook: in 2 volumes / Ed. V.N. Yarygina. - M.; GEOTAR-Media, 2014. - T.1. - 736 p.: ill.

Thus, the genome of organisms contains information about the development of an individual of a certain species and, in addition, there are genes whose expression can lead to the formation of specific germ layers, organs, and tissues. The genotype of the zygote also contains alleles of the parents, which have the ability to be realized in certain characteristics. However, it is known that different levels of regulation of gene expression (remember, for example, alternative splicing) leads to the fact that the activity of even the same genes can result in completely different sets of final products and, as a consequence, a multiplicity of possible development paths.

Old ageAndaging

Old age represents a stage of individual development, upon reaching which the body experiences regular changes in physical condition, appearance, emotional sphere.

Senile changes become obvious and increase in the post-reproductive period of ontogenesis. There are chronological and biological (physiological) ages. According to the modern classification, based on the assessment of many average indicators of the state of the body, people, chronological (passport, calendar ) age who reached 60-74 years old are called elderly, 75-89 years old - old, over 90 years old - centenarians. Exact definition biological age is complicated by the fact that individual signs of old age appear at different chronological ages and are characterized by different rates of increase. In addition, age-related changes in even one trait are subject to significant gender and individual variations.

The state of old age is achieved through changes that make up the content processaging. This process covers all levels of the structural organization of the body - molecular, subcellular, cellular, tissue, organ. The overall result of numerous partial manifestations of aging at the level of the whole organism is an increasing decrease in the viability of the individual with age, a decrease in the effectiveness of adaptive, homeostatic mechanisms.

Signs of aging cordially- vascular systems usually become noticeable after the age of 40. Regular changes are observed in the walls of blood vessels: lipids, primarily cholesterol, are deposited in them, which, along with other structural transformations, reduces elasticity and distorts responses to various stimuli that regulate blood circulation. Typically, the growth of connective tissue in the walls of blood vessels and the heart, replacing working muscle tissue. As a result, the efficiency of the heart decreases and the blood supply to tissues and organs is disrupted. Thus, blood flow through the vessels of the brain of a 75-year-old person is reduced by 20% compared to a 30-year-old person.

At the heart of functional disorders respiratorysystems lies the destruction of the interalveolar septa, which reduces the respiratory surface, the proliferation of connective tissue in the lungs, which reduces the efficiency of aerohematic oxygen exchange. As a result, vital capacity of the lungs decreases with age, which by the age of 75 reaches only 56% of the level at the age of 30.

Easily noticeable change in systemdigestion is tooth loss. The efficiency of the functioning of the digestive glands decreases, and disturbances in the motor (motor) function of the intestines often lead to habitual constipation.

Function suffers during the aging process urinarysystems, the intensity of filtration in the renal glomeruli decreases (by 31% at 75 years of age compared to 30 years of age), as well as the reabsorption of substances from the filtrate in the renal tubules. The deterioration of urinary function is explained by the death with age of a significant number of nephrons (up to 44% of the level at 30 years of age), which are the structural and functional units of the kidneys.

Changes in the aging process deserve special attention muscular system and skeleton. The strength of contractions of the striated muscles decreases, fatigue develops faster, and muscle atrophy is observed. The restructuring of bones characteristic of aging people consists of a thinning of their substance (senile osteoporosis), which leads to a decrease in strength.

During the aging process of the body significant changes occur in reproductive system. At the same time, they affect both main functions of the main organs of the named system - the gonads: the production of gametes and the formation of sex hormones. In women, oogenesis stops when they reach menopause. The formation of functionally complete sperm in the male body is possible, apparently, even in old age.

Changes in the hormonal profile of people due to the decline of reproductive function are complex. There is a widespread opinion about a progressive decrease in the concentration of testosterone in men with age, and in women estradiol and progesterone - the main male and female sex hormones. Let us recall that both types of hormones are produced by organisms of both sexes, only in different quantities. These changes are accompanied by an increase in the secretion of estradiol and progesterone in men and testosterone in women. At the same time, the content of follicle-stimulating hormone in 80-90-year-old women is 14 times higher, and luteinizing hormone - 5 times higher than in 20-30-year-old women. In old people, the ratio of these pituitary hormones is sharply disturbed, which is an important cause of reproductive dysfunction in general. The picture is also complicated by the fact that during the aging process, the tissue response to sex hormones changes due to a reduction in the number of cellular receptors for them.

MANIFESTATION OF AGING AT THE MOLECULAR, SUBCELLULAR AND CELLULAR LEVEL

The molecular and cellular manifestations of aging are diverse. They consist in changes in indicators of information and energy flows, the state of ultrastructures of differentiated cells, and a decrease in the intensity of cell proliferation.

Changes are important during aging body energy, in particular, has long been noted feedback between the lifespan of animals of different species and the specific metabolic rate. There is a special concept energy life potential, reflecting the total amount of energy expended during life. Its value for mammals (except primates) is approximately 924 kJ/g, most primates - 1924 kJ/g, lemur, capuchin monkey and human - 3280 kJ/g body weight. Changes in energy flow during the aging process consist of a decrease in the number of mitochondria in cells, as well as a decrease in the efficiency of their functioning. Thus, in adult rats, the amount of oxygen consumed per 1 mg of mitochondrial protein is more than 1.5 times higher than in old animals. An important property of an aging organism is a shift in the processes of energy supply of the functions of the relationship between tissue respiration and glycolysis (oxygen-free pathway ATP formation) in favor of the latter. Changes in the aging process of cell ultrastructure affect almost all organelles, both general and special.

Listliterature

The abstract is based on the textbook "Regulation of Ontogenesis"

Candidate of Biological Sciences, Associate Professor T.V. Soltys

1. Biology: textbook: in 2 volumes / Ed. V.N. Yarygina. - M.; GEOTAR-Media, 2014. - T.1. - 736 p.: ill.

2. Biology. Guide to practical exercises: training manual. Markina V.V., Oborotistov Yu.D., Lisatova N.G. and others / Ed. V.V. Markina. 2010. -

3. Biology: textbook: in 2 volumes / Ed. V.N. Yarygina. - M.; GEOTAR-Media, 2014. - T.1. - 736 p.: ill.

4. Physiology and fundamentals of anatomy: textbook / Ed. A.V. Kotova, T.N. Loseva. 2011. - 1056 p. (Series "Educational literature for medical students")

5. Histology, embryology, cytology: textbook for universities / Ed. E.G. Ulumbekova, Yu.A. Chelysheva - 3rd ed., - M.: GEOTAR-Media, 2012.

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    Forms, mechanisms, organs, regulation of immunity. Subpopulations of T-lymphocytes, their functions. History of the discovery of regulatory T cells. Efficiency of microbiological diagnostics. Immune regulatory system. The future of transplantology, technical difficulties.

    test, added 05/11/2016

    Characteristics of the stages of ontogenesis of multicellular animals. Features of the embryonic and postembryonic periods of development. Primary organogenesis, differentiation of embryonic cells. Consecutive stages of embryonic development of animals and humans.

    presentation, added 11/07/2013

    Living protoplasm of body cells. Composition of blood hemoglobin. Elements that are found in the human body in relatively large quantities. Processes of excitability and relaxation. The importance of calcium in metabolism. Regulation of water balance.

    presentation, added 01/11/2014

    The concept and biological significance of membranes in the cells of the body, functions: structural and barrier. Their importance in interactions between cells. Desmosome as one of the types of cell contact, ensuring their interaction and strong connection with each other.

1) Levels of ontogeny regulation

Regulation of the expression of all genes occurs at different levels:

1. Regulation on gene level happens in different ways

1.1. DNA modification (for example, replacing cytosine or guanine with methyl-cytosine or methyl-guanine; base methylation reduces gene activity). 1.2. Increasing the volume of DNA in a cell through differential DNA amplification (for example, multiple copies of rRNA genes) or through the formation of polytene chromosomes.1.3. Programmed quantitative changes in DNA (for example, changes in promoter orientation).1.4. DNA splicing (for example, cutting out sections of genes that code for antibodies). 1.5. Chromatin diminution is the irreversible loss of part of the genetic material in the somatic cells of some organisms (ciliates, roundworms, cyclops). 1.6. Changes in the activity of entire chromosomes (for example, inactivation of one of the two X chromosomes in female mammals). 1.7. Changing DNA sequences using mobile genetic elements, such as transposons.

2. Regulation on transcription level– by regulating mRNA transcription. The intensive functioning of individual genes or their blocks corresponds to certain stages of development and differentiation. Transcription regulators in animals are often steroid hormones.

3. Regulation on splicing level(post-transcriptional modification of mRNA) – provides the possibility of the formation of various types of mature, functionally active mRNA. RNA processing is regulated by ribozymes (ribonucleic catalysts) and maturase enzymes. Some human genetic diseases (phenylketonuria, some hemoglobinopathies) are caused by splicing disorders.

4. Regulation on broadcast level– is caused by different activities of different types of mRNA.

5. Regulation on level of post-translational modification of proteins– regulated by post-translational modification of proteins (phosphorylation, acetylation, cleavage of the original polypeptide chain into smaller fragments, etc.).



The considered examples indicate the variety of ways to implement genetic information by regulating the activity of the genes themselves or their products. It should be noted, however, that regulation at the transcriptional level is most economical for the cell, since it prevents the formation of the corresponding mRNAs and proteins when the cell does not need them. At the same time, regulation at the transcription level is relatively slow, while, for example, activation of proteins by cleavage of precursor molecules, although uneconomical, occurs very quickly.

2) Genes regulating the course of ontogenesis

The course of ontogenesis is determined by gene regulatory networks (cascades). They involve signaling proteins and other substances (“morphogens”; secreted by the cell into the surrounding intercellular space), receptors, transcription factors, and small regulatory RNAs. Enhancers (TF binding sites) in the regulatory regions of regulatory genes are an important component of the “genetic development program.” Enhancers determine which switches (and therefore where and when) a given gene will be turned on.

In all animals, a special family of genes, the HOX genes, is responsible for marking the embryo along the anteroposterior axis. First found in Drosophila, then in all animals.

The discovery of similar Hox genes in different types of animals has forced a new look at the morphogenesis of animals and its transformations during evolution. It became clear that by changing one gene or the time (or place) of its inclusion, it is possible to transform, create, remove or transfer to another place an entire organ at once, while maintaining the general structural plan. Hox genes in Drosophila, humans and many other animals are located on the chromosome in a strict order, in the same order in which the differentiation of the main parts of the body of a bilaterally symmetrical animal occurs. First, in the early embryo, the genes responsible for the structure of the organs on the head, then on the chest, begin to work, then the genes begin to shape the tail part.

The Hox gene family is divided into 14 classes. It is believed that these 14 classes arose through the duplication of one or a few original genes, the replicas then mutating and acquiring new functions. Cnidarians and ctenophores have only 4 classes of Hox genes. The putative common ancestor of bilaterally symmetrical animals should have had at least 8. In mammals, all 14 classes are present. The principle of operation of these genes is the same. All of them are transcription factors, that is, their function is to “turn on” or “turn off” other genes. As a result of the work of Hox genes, a cascade of reactions is triggered, leading to the appearance of the necessary proteins in the cell. Later it turned out that in some animals they are not located as correctly as in humans and fruit flies. In addition to Hox genes, there are many other developmental regulators. Most are characterized by pleiotropy. Pleiotropy – multiplicity of functions and phenotypic manifestations. The same regulator gene (TF) can regulate several completely different processes at different stages of embryonic development. These are “professional switches”, which in principle do not care what to switch (if only the regulated gene had the required enhancer). Therefore, in the course of evolution, new “subroutines” can easily come under their control. This is how new signs arise.

So, the course of ontogenesis is regulated by: chronogens, genes of spatial organization (see the manual on genetics)

3) The principle of how genes work in ontogenesis

It is important to note that the process of building an individual of each species begins right from the first division. Consequently, we can say that the development of an individual occurs according to a strict program of cell-by-cell construction, during which step-by-step implementation of genetic information occurs, starting from the first division. The genome reflects precisely the strict cellular sequence of construction of any individual: from the first cell division to the complete formation of the individual, from the first cell, to the second, from it to the 3rd, to the 4th, to the 5th….to the “last”. It is this sequence of construction that is contained in the so-called. “the non-coding part of the genome, called by evolutionists - the “garbage part” of the genome. The study of the works of corresponding member L.I. Korochkin, in particular “Genome, cloning, human origin” (2004), showed that ontogenesis is a strict and unambiguous order of construction individual, which goes through strictly sequential cellular construction, when an embryo is first formed as the initial substrate from stem cells, then it is segmented and the rudiments (“buds”) of the main parts of the body are formed with their further development into semi-finished products, and then into completed organs. Moreover, the entire program (algorithm) for such construction is recorded in the genome along with information about all the characteristics of the individual. Consequently, it can be argued that the construction program is actually information about all organs, members and systems! This is a single and inseparable information. There is no separate information in the genome about the construction plan (program) and separately about “hereditary characteristics”, i.e. on the composition and structure of bodies and members.

I consider the following points to be new and important in describing the structure of the genome and the process of ontogenesis. It seems convenient to divide the entire life program of an individual, implemented by the genome, into 3 large stages:

1st - formation, construction of an individual until birth (first and main part ontogeny programs);

2nd – growth of the individual to maturity (the second important part of the ontogenesis program);

3rd – aging and death.

It seems that they all have their own characteristics and differ greatly in software implementation mechanisms.

The 1st period, the core of ontogenesis, is the most complex programmatically, because it is necessary to build and form closely interconnected, closely intertwined and interdependent all organs, members and systems of different protein content. And its essence is the control of cell-by-cell construction, control of cell division, when each cell’s “fate” is determined: whether it will divide or not, and in the second case, what somatic protein will fill it.

At the 2nd stage, there is actually no need to select protein, because we are talking about the growth of an already formed individual, and it is only necessary to ensure strict proportionality of the growth of all members and organs of the already formed and formed protein structure (maybe with the exception of only the reproductive system). For this purpose, the genome probably contains sections of programs specifically for the growth of all organs and members, as a continuation of the programs for their construction. Apparently, they are all built according to similar algorithms of proportional increase in size and volume and are a continuation of organ building programs. These are also very complex programs, incl. and programs for the proportional growth of toroidal structures such as hollow bones, blood vessels and other structures of enormous complexity. It is known that the growth hormone, the pituitary hormone, plays a major role in the growth process, which largely determines the duration of growth and the final “size” of the individual.

At the 3rd stage, only the process of cell renewal occurs, by replacing them with “new” ones, but of worse quality, probably due to the deterioration in the quality of all processes of expression and cell division, transcription, translation and mitosis in general, caused, as is today believed, by a constant decrease the length of the telomeric ends of chromosomes. Moreover, for each protein somatic tissue, the frequency of renewal is strictly determined, how often it will renew its cells. Brain cells, heart muscles, liver and some others are practically not renewed.

General principles of operation of the program for controlling the formation and construction of an individual in ontogenesis. It seems that the ontogeny program is based on the implementation of 3 basic principles:

The 1st principle is “each cell has its own place”, this is the principle of construction itself: the fate of each cell is predetermined and is implemented through the standard procedure “division - non-division - specialization”. This information is sequentially read from a certain section(s) of the genome and is implemented using the epigenetic mechanism: in the initial position, all genes of the genome are closed with methyl groups and, in accordance with the genome reading program, they are sequentially removed and the desired gene, the next one in the order of cell construction, is activated by the acetylation group histones. Next, this gene is again closed with a methyl group. It is possible that these “closing groups” do not exist on the nails and hair, and they are constantly growing.

2nd principle, the principle of control and increasing the reliability of correct construction: certain control Hox genes (DNA sections) allow construction where it is necessary, in the area of ​​their own responsibility, and prohibit construction where it is not necessary (so that teeth appear in the mouth and did not appear in any other place, the eyes in the previously prepared sockets of the head, and not on the hand, etc.).

3rd principle, the principle of combining programs: because most organs of both humans and animals are very complex, complex in nature and include the simultaneous formation of the bone skeleton, blood vessels, lymph, and various muscle tissues, skin tissues, nerves, tendons, neurons, hair and much more, then all these individual programs are actually integrated into the corresponding cluster, and are, as it were, nested, superimposed on each other. Implementation of the first principle. Because All the organs and members that form a single organism of an individual have a very complex, ornate, but quite definite, strictly specific appearance and shape, then by controlling the process of cell division it is easy to achieve almost any planned shape. This is achieved precisely by the fact that not all emerging cells divide, i.e. there is a process of controlling the direction of division, and, accordingly, the direction of construction of the organ, the formation of its shape. And the fate of each cell, from those just formed at the mitosis phase, in accordance with the general construction plan, is predetermined by the program: will this cell be subjected to differentiation, by expression of the corresponding protein-coding gene in it, or this cell will enter the mitosis phase and undergo further division. It is for this purpose that interphase exists in the process of mitosis with the G1 stage and the critical point R. It is through the corresponding volume of trigger protein synthesis that the further fate of the cell at the R1 point is determined. Those. the amount of this protein determines the further fate of the cell and, thereby, the shape of the created organ or member. If a given cell does not divide, but is subject to specialization, then the contents of the cell, i.e. the type of protein in this specialized cell is known in advance from the purpose of this organ or member.

This sequentially parallel process, this program for realizing the fate of each cell is the actual program of ontogenesis. Consequently, if little trigger protein has been formed in this cell, then this is a signal to start the process of specialization of this cell, and not to divide it. For further specialization, it is necessary to indicate to this cell what its protein content should be, i.e. which protein (or group of proteins during alternative splicing) should be activated in it exactly in accordance with the general plan and general construction program. Obviously, in the process of reading the genome, the amount of trigger protein is determined by the general construction program (ontogenesis) and is encoded by a special DNA control sequence. It is safe to assume that this information is contained in the “non-coding” part of the genome in the zone of dispersed (i.e. scattered) repeating DNA sequences located between genes: their “long” (Line) repeats give the command for the production of trigger protein in large quantities (R is greater than the R threshold), and, as a consequence, the cell enters the division stage. If a short (Sine) sequence follows, then less than the threshold trigger protein is produced and the cell enters the specialization phase. The total number of dispersed DNA sequences in the genome is about 2 million, which is on the same order as the number of fetal cells before birth (about 200 million). Thus, the order of dispersed sequences in the genome determines the order of cell division and specialization, i.e. the order of formation of the shape of an organ. At the same time, the process of activation of these DNA repeats, most quickly, is carried out consistently and formally using epigenetic markers: the removal of repressive methyl groups and the addition of activation groups - acetylation of histones. Therefore, these so-called “non-coding regions of DNA” are coding! They encode not somatic proteins and amino acids, but regulatory proteins and amino acids.

4) Totipotency

TOTIPOTENESS is the ability of individual cells, in the process of realizing the genetic information contained in them, not only to differentiate, but also to develop into a whole organism. Fertilized eggs of plants and animals are totipotent. Animal somatic cells are tissue specific from the early stages of embryonic development and therefore do not have totipotency. However, stem cells in renewing animal tissues within the same tissue type can develop in different directions. For example, stem cells of mammalian hematopoietic tissue give rise to red blood cells and white blood cells. Somatic cells of plants are able to fully realize their development potential with the formation of a whole organism. Specialized cells of various organs (leaf, root, flower) are capable of reproduction in an artificial environment outside the body. When an optimal ratio of phytohormones is created in the nutrient medium, cultured cells can form shoots or transform as a result of somatic embryogenesis into embryo-like structures, which then develop into the whole organism. The ability of plant somatic cells to exhibit totipotency depends on the genotype. The totipotency of somatic cells underlies their use in genetic and cellular engineering. Homeotic mutations in Drosophila. After the formation of segmentation is completed, homeotic genes come into play - a large class of genes that control the development of some part of the body from a certain segment. As a result of homeotic mutation, some other part of the body develops from this segment. Among the homeotic genes, the most famous are Bithorax-Complex (BX-C) and Antennapedia-Complex (Ant-C). In Drosophila, larvae and adults have distinct segments: one cephalic, three thoracic and eight abdominal. Each adult segment contains a set of differentiated morphological structures. The mesothoracic segment bears a pair of wings and a pair of legs, the metathoracic segment carries a pair of legs and a pair of galters - special club-shaped formations that help maintain balance in flight. There is a group of genes responsible for the formation of galters and abdominal segments. One of the genes influencing these processes is BX-C. Without this gene, the embryo develops to a certain stage and then dies. If this organism remained alive, it would have 10 pairs of wings and 10 pairs of legs. The function of the BX-C gene is to inactivate the genes that form the legs and wings in all subsequent segments after the second thoracic segment. The BX-C complex contains three different genes: Ubx, Abd-A and Abd-B. Each of them controls the formation of a specific group of segments. Mutations of these genes cause all subsequent segments to form similarly to one of the previous ones. If all three genes are deleted, only the first thoracic (T1) and ninth abdominal (A9) segments, controlled by other genes, develop normally, all other segments (T3 and all abdominal) develop as T2. If the Ubx gene is preserved, but Abd-A and Abd-B are damaged, all thoracic segments develop normally, and all abdominal segments are represented by the very first - A1. If the Abd-B gene is damaged, all thoracic segments develop normally, then the abdominal segments Al, A2 and A3, and all the rest are formed as the A4 segment.

5) Mechanisms operating during ontogenesis(see Yarygin’s textbook pp. 328-347)

6) Teratogens

Teratogenic effect (from the Greek τερατος “monster, freak, deformity”) - a violation of embryonic development under the influence of teratogenic factors - some physical, chemical (including drugs) and biological agents (for example, viruses) with the occurrence of morphological abnormalities and malformations . Teratogenic factors include drugs, drugs and many other substances. The following features of the influence of teratogenic factors are distinguished:

The effect of teratogenic factors is dose-dependent. The dose dependence of teratogenic effects may vary among different species. For each teratogenic factor there is a certain threshold dose of teratogenic action. Usually it is 1-3 orders of magnitude lower than lethal. Differences in teratogenic effects in different biological species, as well as in different representatives of the same species, are associated with the characteristics of absorption, metabolism, and the ability of the substance to spread in the body and penetrate the placenta.

Sensitivity to various teratogenic factors may change during fetal development. The following periods of human intrauterine development are distinguished. Teratogens are a class of chemical substances or physical effects that have teratogenic properties expressed to varying degrees. These are, first of all, some medications, drugs, alcohol, smoking tobacco and marijuana, cocaine, hormones, and environmental xenobiotics in general (accumulated in huge quantities during technological progress, especially over the last 1-1.5 centuries, alien to the ancient biological structures of living beings chemical substances), not enough is known about the negative effects of many of them on the developing organism. See Thalidomide. Presumably, some dysmetabolic products that occur during diseases of the pregnant mother are also teratogenic. Those substances that do not cause gross physical abnormalities, but can have a negative effect on behavioral, emotional or cognitive processes, and there are apparently much more such substances than teratogens themselves, are called behavioral or psychological teratogenic factors. Teratogens are also ionizing radiation, which can cause mutations during gametogenesis, electromagnetic radiation, and mechanical factors (for example, tight corsets with which women try to hide their pregnancy).

7) Types of developmental defects in humans

Malformations of the central nervous system are classified as polygenic diseases.

Exogenous factors include diabetes mellitus, folic acid deficiency, maternal intake of valproic acid, hyperthermia. Malformations of the central nervous system are also observed in monogenic diseases, for example, Meckel-Gruber syndrome and Roberts syndrome, aneuploidy (trisomy on chromosomes 18 and 13), triploidy and translocations that produce unbalanced gametes. Malformations of the central nervous system also occur in Goldenhar syndrome and OEIS (according to the first letters of the following words: Omphalocele - hernia of the umbilical cord, Exstrophy of bladder - exstrophy of the bladder, Imperforate anus - anal atresia, Sacral abnormalities - malformations of the sacrum).

The main congenital defects of the central nervous system include anencephaly, spina bifida, encephalocele, exencephaly, and spinal canal cleft. They are formed as a result of non-fusion of the neural tube. About 80% of central nervous system malformations are hydrocephalus. It is often combined with other malformations of the central nervous system. Congenital heart defects: Congenital heart defects are often combined with other developmental defects. Concomitant gross malformations are present in every fourth child with congenital heart disease. Children with congenital heart defects have a 10-fold increased prevalence of other developmental defects.

The prevalence of congenital heart defects in newborns is 0.5-1%. 15% of deaths of children under one year of age are due to congenital heart defects. Causes: Genetic factors. Chromosomal abnormalities, mainly trisomies. Monogenic diseases with autosomal dominant and recessive inheritance linked to the X chromosome. 2% of all congenital heart defects are associated with environmental factors. These include, in particular, the rubella virus, as well as drugs such as alcohol, trimethadione and lithium carbonate.

Genetic risk depends on associated malformations and the cause of the disease. If a man suffers from congenital clubfoot (without accompanying defects), the risk of the disease in his siblings and children is about 3%. If a woman is sick, the risk for siblings is about 5%, and for children - 3%.

A diaphragmatic hernia is formed as a result of the movement of abdominal organs (stomach, small intestine, rarely liver) into the chest cavity through a congenital defect of the diaphragm. Congenital dislocation of the hip is one of the most common malformations. It is observed in women 6 times more often than in men. With breech presentation, the risk of this malformation increases 10-15 times. If a woman is sick, the risk for siblings is 3-4%, and for sisters - 10%. If a man is sick, the risk is slightly higher. If the defect was observed in both parents and children, the genetic risk increases to 10-15%.

Gastrointestinal malformations: Pyloric stenosis, Duodenal atresia

(Considered a polygenic disease, although cases of autosomal recessive inheritance have been described), Hirschsprung's disease (congenital aganglionosis of the colon).

8) Embryonic induction

Embryonic induction (from Latin mductio - guidance, excitation) - the influence of one embryonic rudiment (inductor) on the development (differentiation) of another; underlies organogenesis. Manifests itself at all stages of embryonic development. For example, in the blastula, the cells of the area of ​​the future dorsal lip are inducers and influence the development of other parts of the embryo, in particular the notochord.

The notochord, together with the adjacent mesoderm (the so-called chordomesoderm), in turn induces the formation of the nervous system; the part of the brain from which the retina of the eye is formed influences the neighboring portion of the ectoderm, causing its differentiation into the cornea, etc.

Embryonic induction is carried out through direct contact and interaction of groups of cells with each other (surface interaction) or by transmitting the inducing effect through chemical substances that have the properties of low-molecular proteins. The action of inducers, as a rule, lacks species specificity. The phenomenon of embryonic induction was discovered in 1901 by the German embryologist H. Spemann. Embryonic induction is only one of the mechanisms of ontogenesis. Many developmental phenomena require other mechanisms. The area of ​​the dorsal lip of the blastopore, which, when transplanted, causes the formation of mesoderm and neuroectoderm in a new place, is called the “Spemann organizer.” (See Yarygin’s textbook p. 347-353)

8) Persistence is a defect of the embryonic stage of development, consisting in the remainder of embryonic structures after birth.

Atresia- This is a developmental defect consisting in the absence of an opening in an organ.

Stenosis- is a congenital or acquired abnormal narrowing of the lumen of any hollow organ (esophagus, intestines, blood vessel)

Hypoplasia- These are developmental anomalies consisting in underdevelopment of a tissue, organ, part of the body or the whole organism.

Amplification(Latin amplificatio - strengthening, increase), in molecular biology - the process of formation of additional copies of sections of chromosomal DNA, usually containing certain genes or segments of structural heterochromatin. Amplification may be a cell response to selective influence (for example, under the influence of methotrexate). Amplification is one of the mechanisms of activation of oncogenes during tumor development, for example, the N-myc oncogene during the development of neuroblastoma (the most common form of solid tissue cancer in children). Also, amplification is the accumulation of copies of a certain nucleotide sequence during PCR - polymerase chain reaction.

In addition, see pp. 361-364 (Yarygin).

    Realization of hereditary information in the formation of a definitive phenotype.

    Selective gene activity in development.

    Mechanisms of ontogenesis at the cellular and organismal levels.

The main question of biology: How do many different types of cells arise from one egg! And from one genotype – several thousand different phenotypes?

In mammals, more than 1,000 different types of cells are formed from a single zygote.

Karl Marx : “Any development, regardless of its content, can be represented as a series of different stages of development, connected with each other in such a way that one is the negation of the other.”

Development– a continuous process of change, usually accompanied by an increase in weight, size, and change in functions. Almost always involves growth, which may be associated with an increase in cell size or number. The weight of the egg is 1*10x(-5)g, the weight of the sperm is 5x10(-9)g. For a newborn – 3200 g.

An increase in mass alone cannot ensure the formation of characteristics characteristic of the organism.

Stages of development.

Determination of cells

Cell differentiation

Formation of a new form, morphogenesis.

Violation of any stage can lead to developmental defects and deformities.

Determination- limitation, definition – progressive limitation of the ontogenetic capabilities of embryonic cells. This means that at the stage of determination, the cells differ in their morphological characteristics from embryonic cells, but the functions are still performed by embryonic cells. Those. determined cells are not yet capable of performing special functions. In mammals, determined cells appear at the eight blastomere stage. Chimeric, allopheric organisms. Mouse as a research object. Mouse embryos at the 8-blastomere stage are removed using the enzyme pronase and broken down into individual blastomeres, blastomeres from different animals are mixed in a test tube, and then sewn into the uterus. The result is normal animals, but the coloring of the parts is different, because the original forms were of different colors. If such an operation is carried out at later stages of embryogenesis, the animals die, which proves the determination of cells at this stage.

The process of determination is under genetic control. This is a stepwise, multi-stage process that has not yet been studied well enough. Apparently, determination is based on the activation of certain genes and the synthesis of various mRNAs and, possibly, proteins.

Determination may be disrupted, leading to mutations. A classic example is the development of limbs in Drosophila mutants instead of antennae. Formation of limbs in uncharacteristic places.

Differentiation. Determined cells gradually enter the path of development (unspecialized embryonic cells turn into differentiated cells of the body). Differentiated cells, unlike determined ones, have special morphological and functional organizations. Strictly defined biochemical reactions and the synthesis of special proteins occur in them.

Liver cells - albumin.

The epidermal cells of the skin are keratin.

Muscles – actin, myosin, myelin, myoglobin.

Mammary glands – casein, lactoglobulin.

Thyroid gland – thyroglobulin.

The gastric mucosa is pepsin.

Pancreas – trypsin, chymotrypsin, amylase, insulin.

As a rule, differentiation occurs in the embryonic period and leads to irreversible changes in the pluripotent cells of the embryo.

The synthesis of special proteins begins at very early stages of development. Regarding the cleavage stage: blastomeres differ from each other in their cytoplasm. In the cytoplasm of various blastomeres there are different substances. The nuclei of all blastomeres carry the same genetic information, because have the same amount of DNA and identical order of nucleotide pairs. The question of specialization has not yet found an answer.

1939 Thomas Morgan put forward a hypothesis: “cell differentiation is associated with the activity of different genes of the same genome.” It is currently known that about 10% of genes work in differentiated cells, and the rest are inactive. Because of this, different types of specialized cells have their own specific genes. Special experiments on transplanting nuclei from tadpole intestinal cells into a nuclear-free egg have proven that differentiated cells retain genetic material and the cessation of the functioning of certain genes is reversible. The nucleus was removed from the frog egg, and the nucleus was taken from the intestinal cell of the tadpole. Development did not occur; sometimes embryogenesis occurred normally. The structure of an adult frog was completely determined by the nucleus.

The functioning of genes during the development of a multicellular organism is influenced by complex and continuous interactions between the nucleus and cytoplasm and intercellular interactions.

Regulation of differentiation occurs at the level of transcription and at the level of translation.

Levels of regulation of cell differentiation.

    At the transcription level.

Operon system

Participation of proteins - histones, which form a complex with DNA.

Regions of DNA coated with histone are incapable of transcription, while regions without histone proteins are transcribed. Thus, proteins are involved in the control of read-through genes.

Hypothesis of differential gene activity: “The assumption that in different genes of differentiated cells different sections of DNA are repressed (closed for reading) and therefore different types of m-RNA are synthesized.”

    At the broadcast level.

In the early stages of embryonic development, all protein synthesis is provided by matrices created in the egg before fertilization under the control of its genome. mRNA synthesis does not occur; the nature of protein synthesis changes. In different animals, synthesis is activated in different ways. In amphibians, the synthesis of mRNA after the 10th division, the synthesis of t-RNA at the blastula stage. In humans, mRNA synthesis occurs after the 2nd division. Not all mRNA molecules located in the egg are simultaneously used for the synthesis of polypeptides and proteins. Some of them are silent for some time.

It is known that during the development of an organism, the formation of organs occurs simultaneously.

Heterochrony– a pattern that implies non-simultaneous development.

The process of cell differentiation is associated with the depression of certain cells. During gastrulation, gene depression depends on the influence of unequal cytoplasm in embryonic cells. In organogenesis, intercellular interactions are of primary importance. Later, gene activity is regulated through hormonal connections.

In the embryo, different areas influence each other.

If the newt embryo at the blastula stage is divided in half, then a normal newt develops from each half. If the same is done after the onset of gastrulation, one half forms a normal organism, and the other half degenerates. A normal embryo is formed from the half where the dorsal lip of the blastopore was located. This proves that

    cells of the dorsal lip have the ability to organize the development program of the embryo

    no other cells are capable of doing this.

The dorsal lip induces the formation of the brain and spinal cord in the ectoderm. It itself differentiates into the dorsal chord and somites. Subsequently, many neighboring tissues exchange inductive signals, which leads to the formation of new tissues and organs. The function of the induction signal is performed by local hormones that stimulate growth. Differentiation, serve as chemotaxis factors, inhibit growth. Each cell produces a local hormone - kaylon, which inhibits the entry of cells into the synthetic phase of mitosis and temporarily inhibits the mitotic activity of the cells of this tissue and, together with anticaylon, directs the cells along the path of differentiation.

Morphogenesis– formation of a form, adoption of a new form. The formation of a form most often occurs as a result of differential growth. Morphogenesis is based on the organized movement of cells and groups of cells. As a result of movement, cells enter a new environment. The process occurs in time and space.

Differentiated cells cannot exist independently; they cooperate with other cells to form tissues and organs. In the formation of organs, cell behavior is important, which depends on cell membranes.

The cell membrane plays a role in the implementation

Cell contacts

Aggregations.

Intercellular contact– motile cells come into contact and move apart without losing mobility.

Adhesion– cells that come into contact are pressed against each other for a long time.

Aggregation – Special connective tissue or vascular structures arise between adherent cells, i.e. simple cellular aggregates of tissues or organs are formed.

For the formation of an organ, the presence in a certain number of all cells that have a common organ property is necessary.

Experiment with disaggregated amphibian cells. 3 tissues were taken: the epidermis of the neural plate, a section of the neural folds, and intestinal ectoderm cells. The cells are randomly disaggregated and mixed. The cells begin to gradually be sorted. Moreover, the sorting process continues until 3 tissues are formed: on top is a layer of epidermal tissue, then the neural tube, and below is a cluster of endodermal cells. This phenomenon is called cell segregation - selective sorting.

Cells of eye buds and cartilage were mixed. Cancer cells are not capable of segregation and are inseparable from normal ones. The remaining cells are subject to segregation.

Critical periods of development.

Critical period– a period that is associated with changes in metabolism (genome switching).

In human ontogenesis there are:

1. development of germ cells

2. fertilization

3. implantation (7-8 weeks)

4. development of axial organs and formation of the placenta (3-8 weeks)

5. stage of brain growth (15-20 weeks).

6. formation of the main functional systems of the body and differentiation of the reproductive apparatus (10-14 weeks).

7. birth(0-10 days)

8. period of infancy – maximum intensity of growth, functioning of the energy production system, etc.

9. preschool (6-9 years old)

10. puberty - for girls 12. for boys 13 years old.

11. end of the reproductive period, for women - 55, for men - 60 years.

Mutations appear during critical periods of development, so you need to be attentive to these periods. All genetic programs are associated with children's institutions.

Hereditary defects (deformities) are caused by changes in the parents during gametogenesis in the genotype.

Hereditary deformities are expressed due to damaging environmental factors.

About 50 forms of hereditary deafness have been described. About 250 eye anomalies, about 100 skeletal anomalies.

The immune, endocrine and nervous systems are of great importance in the development of the body.

The immune system contributes to the preservation and origin of life, controls genotypic constancy, and performs control functions. In the early stages of embryogenesis, it is formed from stem cells.

The thymus develops up to 2 months of age and fades away by puberty.

The immune system cleanses the body of mutating genotypes.

The development of organisms is based on a genetic program (embedded in the chromosomal apparatus of the zygote) and occurs under specific environmental conditions, and at different stages of ontogenesis, gene activity depends on both internal and external factors.

As a result of the embryonic stage of ontogenesis, an organism is formed that undergoes further stages ontogenesis changes. (growth, development)

Remember: The influence of alcohol and nicotine on the chromosomal apparatus of germ cells.

1) newborn (1-21 days);

2) infancy (21 days - 1 year);

3) early childhood (1–3 years);

4) preschool period (4–7 years);

5) junior school age (8-12 years for boys, 8-11 years for girls);

6) prepubertal period (12–15 years);

7) adolescence (15-18 years);

8) adolescence (18-21 years)

9) mature age:

I period (22–35 years for men, 22–35 years for women);

II period (36–60 years for men, 36–55 years for women);

10) old age (61–74 years for men, 56–74 years for women);

11) old age (75–90 years);

12) long-livers (90 years and above).

1) Acceleration in children since the 2nd half of the 20th century

2) During the embryonic period.

The embryo of mammals, including humans, is very sensitive to the effects of unfavorable environmental factors. Its development is influenced by substances that it receives from the mother’s blood (for example: 1 smoked cigarette reduces the supply of O2 by 10 times; the fetal liver is not able to eliminate toxic substances and therefore accumulates in the tissues; alcohol has a strong effect on the central nervous system)

environmental factors(temperature, light, pressure, gravity, food composition by content chemical elements and vitamins, various physical and chemical factors) radiation, ultrasound, vibration, electromagnetic field

3) social factors.

4) for example, the regulation of metamorphosis in amphibians, during which many different changes occur in the body. Some organs (tadpole larvae) are destroyed, others (organs of an adult frog) grow and develop rapidly. All these changes occur under the influence of thyroid hormone. Amphibian larvae lacking a thyroid gland do not undergo metamorphosis (however, it can be induced in operated larvae if a hormone is injected into them).

The role of hormones is especially clear in numerous examples of disorders in the activity of the endocrine glands in humans, well known to doctors. Thus, with excessive production of growth hormone, giants of two and even three meters in height can develop. In case of insufficient secretion of this hormone, people become dwarfs (height - from 60 to 140 cm).


39. Genetic regulation of development, features of molecular genetic processes at different stages of ontogenesis (genetic determination of development, differential activity of genes, influence of ooplasmic segregation, T-locus, genes of puberty, aging).

It's obvious that genetic control of development exists because the set of genes received by the body during fertilization ensures the development of an individual of a specific biological species from the zygote ( species specificity of ontogenesis).

Determination is a set of factors that determine the natural nature of formative processes, or the influence of one part of the embryo on its other parts, inducing these latter to undergo suitable conditions a fragment of the path of its normal development.

The genetic basis of cell differentiation is explained by the hypothesis of differential gene activity.
 According to it, differences in the spectrum of proteins produced by differentiating cells reflect differences in the set of active genes. In cells of any direction of specialization, there are, as it were, 3 groups of active genes: - those that control the fundamental processes of cell life and are active in all living cells; - those that determine similar features of cells of the same tissue; - control features specific to cells of a particular type

Ooplasmic segregation is the occurrence of local differences in the properties of the ooplasm, which occurs during periods of growth and maturation of the oocyte, as well as in the fertilized egg. S. is the basis for subsequent differentiation of the embryo: during the crushing of the egg, sections of the ooplasm that differ in their properties enter different blastomeres; interaction with them of identically potent cleavage nuclei leads to differential activation of the genome. In different animals, S. does not occur simultaneously and is expressed to varying degrees.

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