Early Embryogenesis and Developmental Biology PDF

Early Embryogenesis and Its Molecular Basis ABI 3109 – Developmental Biology Department of Biological Sciences Summary of Embryogenesis CLEAVAGE ⚫ a succession of rapid mitotic divisions whereby enormous volume of egg cytoplasm is divided into smaller nucleated cells ⚫ results in the...

Early Embryogenesis and Its Molecular Basis ABI 3109 – Developmental Biology Department of Biological Sciences Summary of Embryogenesis CLEAVAGE ⚫ a succession of rapid mitotic divisions whereby enormous volume of egg cytoplasm is divided into smaller nucleated cells ⚫ results in the formation of blastomeres ⚫ also called blastulation ⚫ result of 2 coordinated processes: ⚫ karyokinesis ⚫ cytokinesis Mitosis Promoting Factor (MPF) ⚫ Causes cell to enter M phase ⚫ MPF activation causes ⚫ Chromosome condensation ⚫ Nuclear envelope breakdown ⚫ RNA polymerase inhibition (shutdown transcription) ⚫ Myosin regulatory subunit phosphorylation (inhibit cytokinesis) Mitosis Promoting Factor (MPF) ⚫ transition from fertilization to cleavage ⚫ responsible for meiotic cell division in the egg cell ⚫ has 2 subunits: ⚫ cyclin B ⚫ cyclin-dependent kinase (cdk2) Mitosis Promoting Factor It is cyclin B that undergoes a cell cycle specific synthesis and degradation regulated by the cells nucleus to control the cell cycle in normal somatic cells Patterns of Embryonic Cleavage ⚫ Factors in cell specialization ⚫ Intrinsic factor(lineage)- information is inherited from the mother cell, as a result of cell division ⚫ Extrinsic factor (positional)- is received from the cell’s surrounding environment or from neighboring cells Patterns of Embryonic Cleavage ⚫ Determining the Body Axes:  Cytoplasmic Determinants(mom’s genome)- either mRNAs or proteins that are found in the egg prior to fertilization  Cytoplasmic determinants are a key feature of protostome development and some deuterostomes, Example is the factor bicoid (present in a concentration gradient across the unfertilized egg)- anterior vs posterior Patterns of Embryonic Cleavage ⚫ Determining the Body Axes:  Yolk Polarity - occurs in the eggs of animals which have large amounts of yolk in their eggs Animal pole Anterior Vegetal pole Posterior Patterns of Embryonic Cleavage ⚫ Determining the Body Axes:  Induction- cell to cell communication that leads to different cell fates among initially identical cells mammalian embryos have no cytoplasmic determinants and have very small amounts of evenly-distributed yolk Various Patterns of Cleavage Basis of the following types of cleavage:  Cleavage Furrow - Holoblastic and Meroblastic Cleavage  Fate of Germ Layer - Indeterminate and Determinate Cleavage  Planar Division/Arrangement of the Cell - Bilateral, Radial, Spiral Rotational Cleavage  Basis of Cleavage Furrow ⚫ HOLOBLASTIC – complete cleavage ⚫ Holoblastic Equal in microlecithal and Isolecithal eggs(blastomeres of equal size) ⚫ Holoblastic Unequal in mesolecithal eggs (unequal blastomere-micromere and macromere formation) ⚫ MEROBLASTIC – incomplete cleavage ⚫ Superficial meroblastic-centrolecithal eggs, the cleavage is restricted to the peripheral cytoplasm of the egg ⚫ Discoidal meroblastic- macrolecithal egg, cleavage furrows can be formed only ithe disc-like animal pole region.-  Basis of Planar Division ⚫ Radial - division planes at 90 degree angles relative to each other blastomeres aligned directly over or to the side of one another ⚫ Spiral - division planes not at 90 degree angles ⚫ Bilateral - when cleavage activity is the same on both sides, creating left and right halves ⚫ Rotational - The first cleavage is a normal meridional division, however, in the second cleavage, one of the two blastomeres divides meridionally and the other divides equatorially Radial vs Rotational  Basis of Fate of Germ Layer ⚫ Determinate - cells whose future differentiation pathways are determined at an early developmental stage resulting in specialization ⚫ Indeterminate -results in cells that can each develop into a full organism if separated PATTERNS OF EMBRYONIC CLEAVAGE PATTERNS OF EMBRYONIC CLEAVAGE PATTERNS OF EMBRYONIC CLEAVAGE Midblastula transition ⚫ Activation of Zygotic Gene Transcription - zygote starts producing its own mRNAs that are made from its own DNA, and no longer uses the maternal mRNA - expression of paternal genes is first observed ⚫ Cell Cycle Changes - the cell cycle begins to slow down and the G1 and G2 phases are added - asynchronous cell division ⚫ Cell migration - central process in the development and maintenance of multicellular organisms Cleavage in Fish Eggs ⚫ discoidal and meroblastic ⚫ occurs in the blastodisc ⚫ calcium ions – construction of actin cytoskeleton ⚫ 15 mins per division Midblastula transition ⚫ gene transcription ⚫ slow cell division Cleavage in Fish Eggs Distinct cell populations ⚫ YSL – yolk syncytial layer ⚫ directs some movements of cell in gastrulation ⚫ EVL – Enveloping layer ⚫ most superficial ⚫ becomes periderm (from extraembryonic covering) ⚫ Deep Cells ⚫ between EVL and YSL ⚫ give rise to embryo proper Distinct cell populations Amphibian Cleavage ⚫ radially symmetrical; holoblastic unequal ⚫ animal pole and vegetal pole = polarity ⚫ formation of morula (16-64 cell stage) ⚫ blastocoel apparent in 128-cell stage Amphibian Cleavage Amphibian Cleavage Cleavage in Birds Eggs ⚫ discoidal meroblastic; telolecithal ⚫ occurs in the blastodisc ⚫ 1st cleavage furrow – centrally ⚫ equatorial and vertical cleavages divide the blastoderm  Cleavage in Birds Eggs ⚫ subgerminal cavity ⚫ space between the blastoderm and yolk ⚫ area pellucida ⚫ forms most of the actual embryo ⚫ area opaca ⚫ peripheral ring of blastoderm that have not shed their deep cells ⚫ marginal zone ⚫ between the area opaca and area pellucida Cleavage in Birds Eggs Cleavage in Mammals ⚫ meridional and equatorial (rotational cleavage) ⚫ blastomeres do not divide at the same time Cleavage in M a m m al s ⚫ smallest and slowest (human 100µm) ⚫ cells do not increase exponentially ⚫ blastomeres do not divide at the same time Cleavage in M a m m a l s Compaction ⚫ blastomeres maximize contact with one another forming compact ball of cells Morula ⚫ large group of external cells and small internal cells Cavitation ⚫ process of formation of internal cavity of morula ⚫ trophoblast secretes fluid into the morula  Compaction at 8 cell stage and Morula formation at 16-32 stage cell Cell adhesion(e-cadherin) protein is formed and blastomere pull tightly together (Compaction) Cells continue to divide forming inner and outer cells (morula) Cavity is formed due to secretion of fluid to create blastocoel (Cavitation) Blastocyst is being formed which is embed in the uterus and establish a placenta Cleavage in M a m m a l s ⚫ Trophoblast ⚫ forms the tissue of chorion ⚫ cells contain integrin binds with uterine collagen, fibronectin & laminin ⚫ secrete proteases ⚫ ICM – inner cell mass ⚫ gives rise to embryo and yolk sac, allantois and amnion ⚫ supports the trophoblast Human Cleavage ⚫ measured in days compared to other vertebrates ⚫ 2 cell stage = 1 day ⚫ 4-cell stage = 2 days ⚫ 16-cell stage = 3 days ⚫ blastocyst = 4 days ⚫ with trophoblast and ICM = 5 days Human Cleavage ⚫ human egg has no plenty of stored ribosomes and RNA during oogenesis; embryo must rely on gene products ⚫ Oct4 gene is important in early development ⚫ small amount of maternal mRNA in embryos ⚫ transcription products from maternal and paternal chromosomes guide the early development  Blastocyst Attachment Zona pellucida disintegrate (strypsin) having exposed to uterine wall ready to attach Integrins in trophoblast cells attach to collagen, laminin, fibronectin (endometrium) -protein digesting enzymes enable blastocyst to bury into wall Tissue Formation of Early Mammalian Embryo Trophoblast provide nutrient and develop into a large part of placenta Decidua is uterine lining that forms maternal placenta (progesterone) Tissue Formation of Early Mammalian Embryo Cytotrophoblast (layers of langerhans) inner layer Syncytiotrophoblast is epithelial covering of embryonic placental villi that invades the wall of the uterus to establish nutrient circulation between the embryo and the mother  Tissue Formation of Early Mammalian Embryo Mesodermal tissue extends outward from embryo – from yolk sac and primitive streak derived cells Connecting stalk of extraembryonic mesoderm connecting embryo to trophoblast forms vessels of umbilical cord Development After Implantation Figure 16.16 Cleavage in Mammals Molecular Basis for Embryo Devt ⚫ Transcription factors ⚫ proteins with domains that bind to DNA of promoter / enhancer region of specific genes ⚫ interacts with RNA polymerase 2 thereby regulating amount of mRNA and gene products Transcription factors ⚫ Homeobox ⚫ nucleotides that encode for homeodomain ⚫ Homeobox genes code for transcription factors that activate gene regulation (i.e. segmentation and axis formation) ⚫ Hox genes Transcription factors ⚫ Hox genes ⚫ homoebox gene complex (humans & other vertebrates) ⚫ with 39 homologous homeobox genes ⚫ loss of function; gain of function ⚫ cranial to caudal patterning ⚫ antennapedia – controls placement of legs ⚫ bithorax – abdominal and posterior thoracic segments Transcription factors ⚫ Pax genes ⚫ roles in sense organs and developing NS Pax Protein Family Transcription factors ⚫ Sox genes ⚫ family of transcription factors with common HMG (high mobility group) domain ⚫ binds to several nucleotides and cause pronounced conformational change (e.g. SRY gene) Transcription factors ⚫ Basic helix-loop-helix proteins ⚫ class of transcription factor with short stretch of amino acid in which 2 alpha helices are separated by an amino acid loop ⚫ regulate myogenesis Transcription factors ⚫ Zinc finger protein (ZnF) ⚫ family of transcription factor with cysteine and histidine are bound by zinc ions to cause the polypeptide chain to become finger like ⚫ binding of DNA, RNA and proteins Transcription factors ⚫ Lim proteins ⚫ bind to DNA nucleus ⚫ absence causes headless mammalian embryos ⚫ T box genes ⚫ induce mesoderm layer and specification of forelimb and hindlimb Transcription factors ⚫ Dlx gene - patterning of outgrowth parts - appendage development - morphogenesis of jaws and inner ear ⚫ Msx gene ⚫ Embryonic development of the epitheliomesenchymal interactions in the limbs and face ⚫ are general inhibitors of cell differentiation in prenatal development ⚫ postnatal life they maintain the proliferative capacity of tissues Molecular Basis for Embryo Devt ⚫ Signaling molecules ⚫ also known as cytokines ⚫ effect neighboring cells or distinct cells ⚫ members of growth factors ⚫ bind as ligand to receptor molecules  TGF – β family ⚫ consists of 30 molecules ⚫ mesodermal induction, myoblast proliferation ⚫ activin – granulosa cell proliferation ⚫ decapentaplegic – signaling limb development ⚫ left – determination of body symmetry ⚫ Sonic hedgehog (Shh) – affect gene expression of target cell Transforming growth factor beta (TGF-β) is a multifunctional cytokine -produced by all white blood cell lineages Fibroblast growth factors (FGFs) are broad-spectrum mitogens and regulate a wide range of cellular functions  including migration  proliferation  differentiation  Survival It is well documented that FGF signaling plays essential roles in development, metabolism, and tissue homeostasis FGF family ⚫ FGF-1 – keratinocyte proliferation; liver induction ⚫ FGF-2 – hair growth; incduction of renal tubule ⚫ FGF-3 – inner ear formation ⚫ FGF-4 – trophoblast mitotic activity ⚫ FGF-5 – ectodermal placode formation ⚫ FGF-8 – midbrain patterning; limb outgrowth, teeth induction, filiform papillae induction ⚫ FGF-10 – limb induction; prostate gland morphogenesis