Topic: MOLECULAR GENETIC MECHANISMS OF ONTOGENESIS. DISORDERS OF ONTOGENESIS AND THEIR PLACE IN HUMAN PATHOLOGY Plan 1. Ontogenesis, its periodization. 2. Embryonic development, its stages. Provisional organs. 3. Molecular and cellular mechanisms of differentiation. 4. Differentiation of embryonic leaves and tissues. Embryonic induction. 5. Critical periods of human embryonic development. Teratogenic environmental factors. 6. Congenital malformations, their modern classification: hereditary, exogenous, multifactorial; embryopathy and fetopathy; phylogenetically determined and non- phylogenetic. 7. Postembryonic human development and its periodization. Neurohumoral regulation of growth and development. 8. Aging as a stage of ontogenesis. Theories of aging. The concept of gerontology and geriatrics. 9. Clinical and biological death. Recommended literature: 1. Medical Biology : text-book / Bazhora Yu. I., Bylyk R. Ye., Chesnokova M. M. et al. 2nd ed., revised and updated. Vinnytsia : Nova Knyha, 2019. 448 p. 2. Organismic level of life organisation. Bases of human genetics. Training text-book on Medical biology (module II) for students of medical and stomatological faculties / Dubinin S.I., Ovcharenko O.V., Vatsenko A.V. et al. Poltava, 2014. 78 p. 3. Lazarev K.L. Medical Biology: Text-book. Second edition. – Simferopol: IAD CSMU, 2003. 592 p. 4. Medical biology: The study guide of the practical classes course / O.V. Romanenko, O.V. Golovchenko, M.G. Kravchuk, V.M. Grinkevych. Edited by O.V. Romanenko. – K.: Medicine, 2008. 304 p. 5. Bekish O.-Y.L. Medical biology: Textbook for students of higher educational establishments. Vitebsk: VSMU Press, 2003. 346 p. 6. Green N.P., Stout G.W., Taylor D.I. Biological Science. Cambridge, 1994. 7. Kimball, John W. Cell biology. Addison-Wesley Publishing company, Inc, 1984. Ontogenesis (the individual development of an organism) Ontogenesis (also, ontogeny from the Greek – «ontos» – «being, existence» + «genesis» – «origin») is the set of morphological, phisiological and biochemical transformations from the moment of germing up to death; the entirety of an organism's lifespan. Ontogeny is the developmental history of an organism within its own lifetime, as distinct from phylogeny (from the Greek phyla, meaning «tribe» and genesis meaning «origin»), which refers to the evolutionary history of a taxon (species): individual organisms develop (ontogeny), while species evolve (phylogeny). Recapitulation theory • «ontogeny recapitulates phylogeny» (Ernst Haeckel,1866): embryonic development (ontogeny) repeats phylogeny (the genealogy of the species). • It means, we pass through some (not all) of the embryonic stages that our ancestors passed through. Ernst Haeckel 1834–1919 Analogous and homologous structures • Same structure, different functions • Show common ancestor • Different structure, similar functions • Evidence of common environmental demand Rudiments (vestigial structures) remains of structures / organs, that once had an importance in ancestor’s organism and no longer useful Vestigial Human Parts: • Gill slits – once used to breathe oxygen in water • Yolk sac – once used to nourish developing embryo • Tailbone – once used for balance • Appendix – once used to digest plants • Wisdom teeth – once used to grind plant tissue, etc. • Human has up to 90 Darvin’s tubercle vestigial structures • Evidence Conclusion: Indicates common ancestry Atavisms reappearence of ancestral traits after they have been lost in previous generations Atavisms in humans: • Human tails • Supernumerary nipples in humans (and other primates) • Hypertrichosis • Color blindness in humans Types of ontogenesis in animals: 1. larval type: development of an organism by metamorphosis – the change of shape or structure of organism from one developmental stage to another. Example: mosquito: ovum – larva – pupa – imago; louses: ovum – larva – imago; pincers: ovum – larva – nymph – imago. 2. non-larval type: formation of an organism in an egg (reptiles, birds). 3. intrauterine ontogenesis: development of an organism inside a maternal organism (mammals). Prezygotic (pre-embrionic = progenetic) period Progenesis – is a period of maturation of specialized generative cells – gametes. This maturation process is called spermatogenesis in males and oogenesis in female. Main stages of prenatal period: 1)Pre-embrionic (weeks 1-2) 2)Embryonic (weeks 3-8) 3)Fetal (weeks 9-38) Main processes of prenatal period: • Fertilization is fusion of a female and male gamete with forming of zygote: ♀ gamete (n) + ♂ gamete (n) = zygote (2n) • Cleavage is the series of rapid cell divisions of the zygote with the formation of blastula (2-8 cells), morula (solid ball of 12- 16 cells) and blastocyst (hollow ball of many calls with inner cavity – blastocoel): zygote → blastula → morula → blastocyst • Gastrulation is the process of formation in embryo the three germ embryonic layers (ectoderm, mesoderm and endoderm): blastocyst → gastrula + extraembryonic membranes • Histogenesis • Organogenesis The stages of pre-embryonic development: fertilization → implantation (the 1st week of ontogenesis) Fertilization Kinds of cleavage corresponds to the type of egg by yolk distribution I. Holoblastic (complete) cleavage II. Meroblastic (incomplete) cleavage A. Isolecithal (sparse, evenly distributed yolk) A. Telolecithal (dense yolk throughout most • Radial cleavage of cell) (echinoderms, hemichordates) • Bilateral cleavage (cephalopod • Spiral cleavage (annelids, molluscs) most mollusks, flatworms) • Discoidal cleavage (some fish, reptiles • Bilateral cleavage (tunicates) and birds) • Rotational cleavage (placental B. Centrolecithal (yolk in center of egg) mammals, nematodes) • Superficial cleavage (most insects) B. Mesolecithal (moderate vegetal yolk disposition) • Displaced radial cleavage (amphibians, some fish [the lampreys, gars and bowfins) The cleavage of human zygote In a man the cleavage of zygote is holoblastic, rotational and asynchronous: • In Holoblastic cleavage the zygote and blastomeres are completely divided during the cleavage, so the number of blastomeres doubles with each cleavage. • Rotational cleavage involves a normal first division along the meridional axis, giving rise to two daughter cells. The way in which this cleavage differs is that one of the daughter cells divides meridionally, whilst the other divides equatorially. • Mammals display rotational cleavage and an isolecithal distribution of yolk (sparsely and evenly distributed). Because the cells have only a small amount of yolk, they require immediate implantation onto the uterine wall in order to receive nutrients. • Mammals have a slow rate of division that is between 12 and 24 hours. These cellular divisions are asynchronous. Cleavage is the series of rapid cell divisions of zygote without increasing in size with the formation of morula (solid ball of 12-16 cells) and blastocyst (hollow ball of many cells with inner cavity – blastocoel). Blastomeres: • cells of blastula • genetically equal • have identical developmental potency (not differentiated) • so each of them can give rise to a new individual • their sizes decrease during cleavage as they continue to be retained within the zona pellucida of an egg Blastocyst The stage with a cavity inside that is filled with fluid, 2 different cell populations: trophoblast + inner cell mass (embryoblast), during the day 5 Gastrulation is the reorganizing of single- layered blastula into a multilayered structure – gastrula: • the main body axis and polarity begin to become apparent (dorsal-ventral, anterior- posterior); • cell migrations to positions where they will form the three germinal cell layers: ectoderm, mesoderm and endoderm; • develops on 7 th day and lasts to the end of the 2nd week after fertilization. Types of Cell movement in Gastrulation → In human the gastrulation occurs by type of delamination ! The germinal layers give rice to various tissues and organs of animals (histo- and organogenesis): Endoderm: Mesoderm: Ectoderm: digestive tract, lungs, liver, connective tissue, bones, muscles, skin (epidermis), hair, nails, the pancreas, thyroid gland, urinary dermis, heart, blood vessels, gonads, eye lens, the pituitary gland, bladder excretory organs (kidneys) and the the epithelium of the nasal notochord (the dorsally located cavity, mouth, anal canal, supportive rod of all chordates) nervous system, sense organs Provisional organs (extraembryonic membranes) • are temporary organs formed by the embryo during embryogenesis and which ensure its growth and development. • include the chorion, amnion, placenta, allantois, yolk sac, umbilical cord. Extraembryonic membranes: • amnion – originates from epiblast, forms an amniotic membrane that produces amniotic fluid, which creates the aqueous environment for embryo development; • chorion (chorionic villi) – originates from trophoblast, surrounds embryo and all other membranes, penetrates the lining of the uterus and forms the placenta with it; • yolk sac – originates from hypoblast, site of early blood cell formation, actively involved in the nutrition and respiration of embryo, but 8 weeks later undergoes a reversal; • allantois (urinary sac) – outpocketing of embryo’s gut, incorporated into umbilical cord, is an organ of nutrition, gas exchange and excretion in the early stages of embryonic development, and in the 2nd month of embryogenesis is reduced. Placenta • placenta is a special organ that: • provides the fetus with nutrients and oxygen, absorbs the end products of metabolism,