The Early Development of Vertebrates: Birds, and Mammals Chapter 9

This Final Chapter on the Process Amniotes Those vertebrates whose embryos form an amnion (water sac) Birds and reptiles form similar patterns of development Vertebrate; birds, reptiles, and fish are by Meroblastic Cleavage Mammals however are by Holoblastic Cleavage Modified to make a placenta

Cleavage Patterns 5.3 Summary of the main patterns of cleavage

Early Mammalian Development

Cleavage Cleavage in Mammals Difficult to study because Mammalian eggs are among the smallest in the world Hard to experiment with (manipulate) Human zygote 100 nm in diameter 1/1000 size of frog embryo Not produced in large numbers Fertilization/development dependent on taking place inside another living organism

Unique Nature of Mammalian Cleavage Unique nature of mammalian cleavage starts prior to fertilization Mammal egg wrapped in cumulus cells as it is released from ovary Swept by fimbriae into oviduct Fertilization at this region or in ampulla Region closest to ovary Meiosis is completed after sperm entry 1st cleavage begins ≈ 1 day later

Unique Nature of Mammalian Cleavage 8.15 Development of a human embryo from fertilization to implantation

Unique Nature of Mammalian Cleavage Cleavage in mammals is among the slowest of all in animal kingdom 12-24 hours apart Cilia in oviduct propel the embryo toward the uterus It is during this time cleavage starts and continues slowly Mammals have a unique orientation of blastomeres in relation to one another

Unique Nature of Mammalian Cleavage 1st cleavage Normal meridional division 2nd cleavage Different One divides meridional Other divides equatorially Called Rotational cleavage 8.16 Comparison of early cleavage in (A) echinoderms and amphibians and (B) mammals

Unique Nature of Mammalian Cleavage Mammalian blastomeres do not divide at same time Asynchrony Do not increase exponentially (2..4..8..16...) normal synchronous Frequently odd numbers Mammalian genome is activated during early cleavage As soon as nuclei is formed Not maternal cytoplasm Mouse, goat  switches from maternal to zygote control at 2 cell stage Humans  switch at 4 to 8 cell stage

Compaction Compaction Most studies focus on mouse Easily bred Large litters Compaction Mouse blastomeres through 8 cell stage form a loose arrangement with plenty of space between them Then cell adhesion molecule E-cadherin starts to be expressed Begin to group together into a compact ball of cells

Compaction 9.20 Cleavage of a single mouse embryo in vitro

Compaction Begin to group together into a compact ball of cells Morula This is unique to mammalian cleavage Stabilized by tight junctions, sealing off the inside of the sphere Inside cells form gap junctions – ions pass Morula 16 cell compacted from 8 cell compact group Small inner cells surrounded by large outer cells (external cells) Early blastomeres (8-cell stage) can form both trophoblast cells or embryo precursor cells

Cleavage and Compaction

Compaction External cells become Trophoblast First divisions Also called trophectoderm They form chorion tissue – allows O2 and nourishment (non-embryo forming cells) Secretes hormones (-HCG) for uterus to keep embryo First divisions To make cell that stick to uterus Trophoectoderm is first differentiation in mammals Adhere to uterus Digest path into lining

Compaction Embryo is derived from inner cells of 16 cell stage and some divisions off of the outer cells Migrating inside Called Inner Cell Mass (ICM) at 32 cell stage Give rise to embryo, allantois, yolk sac, amnion 64 cell stage Trophoblast separate from inner cell mass Do not contribute cells to the other now Inner cell mass secretes proteins to make trophoblast divide (Fgf4) These cells were totipotent ≡ capable of everything – from early blastomere Inner cells are pluripotent ≡ capable of many things

Compaction Cells of these 2 regions express different genes ICM (Inner cell mass) Secrete signals to remain Pluripotency Cells divide to become embryonic stem cells Morula does not have internal cavity

Compaction Cavitation As blastocoel expands Called Blastocyst Trophoblast secrete fluid into morula to create blastocoel Has Na+/K+ and Na+/H+ pump Pump natural central cavity Osmotically drains in water As blastocoel expands Inner cell mass positions one side of the trophoblast cell ring Called Blastocyst

Formation of the Blastocyst Cavity

Cleavage and Compaction

Developmental Potential of the Inner and Outer Cell Masses

Escape from the Zona Pellucida While it moves through oviduct to uterus Blastocyst expand within Zona pellucida Zona pellucida prevents cells from adhering to oviduct walls If this happens in humans – it is called a ectopic pregnancy Also called a “tubal” pregnancy Life-threatening !!!!

Escape from the Zona Pellucida Later embryo breaks through Zona pellucida (ZP) and can now adhere to the uterine wall Called Hatching from ZP Digesting small hole and squeezing through Using Trypsin like protease Once they make direct contact with the uterus

Escape from the Zona Pellucida 9.21 Hatching from the zona and implantation of the mammalian blastocyst in the uterus

Mammalian Female Reproductive Tract and Early Development

Escape from the Zona Pellucida Endometrium (Uterine epithelium) “Catches” blastocyst Using extracellular matrix of collagen, sugars, laminin, fibronectin, hyaluronic acid receptors First attachment mediated by L-selectin on trophoblast cells – adhering to sulfated polysaccharides on uterus cells Sulfated polysaccharides synthesized in response to corpus luteum – secretion of estrogen and progesterone Other adhesion systems then coordinate to keep blastocyst

Escape from the Zona Pellucida Trophoblast secretes a set of proteases once it contacts the uterus These are protein-digesting enzymes Collagenase, Stromelynsin, Plasminogen activator Digest through uterine tissue Enabling the blastocyst to bury itself within the uterine wall

Mammalian Gastrulation Similarities exist between birds and mammals Some believe this is due to being descendants of reptiles ? (This is believed by evolutionary theory supporters, only!!) Both have parallel developments useful in studying Gastrulation similar even in absence of large yolk in mammals

Modification for Development with Another Organism Mammals obtain nutrients directly from its mother Fetus uses organ to obtain/absorb maternal nutrients Chorion Derived primarily from embryonic trophoblast cells with supplemental mesodermal cells Forms the fetal portion of the placenta It induces maternal portion formation Maternal portion called Decidua This is rich in O2 and nutrients from mother

Modification for Development with Another Organism Origins of mammalian tissue development summarized: First segregation of cells within Inner cell mass from trophoblast Forms 2 layers 2 layers Hypoblast (lower) layer Sometimes called primitive endoderm Epiblast above the inner mass Whether a cell becomes upper or lower does not depend on its position in ICM Only expression of Nanog or Gata6 transcription factors

Cleavage and Compaction

Modification for Development with Another Organism 9.24 in 10th edition Schematic diagram showing the derivation of tissues in human and rhesus monkey embryos

Modification for Development with Another Organism 9.24 Tissue formation in the human embryo between days 7 and 11

Modification for Development with Another Organism 9.24 Tissue formation in the human embryo between days 7 and 11

Modification for Development with Another Organism Epiblast and hypoblast form Bilaminar germ disc Hypoblast ( primitive endoderm) cells delaminate from inner cell to Line the blastocoel cavity Form extraembryonic endoderm Forms yolk sac No part of embryo

Modification for Development with Another Organism Epiblast splits to form Embryonic epiblast Other cells of epiblast line amnionic cavity And form the Amniotic ectoderm Amnionic fluid fills cavity Shock absorber for embryo Prevents drying out Similar to avian

Modification for Development with Another Organism 9.26 Amnion structure and cell movements during human gastrulation

Modification for Development with Another Organism Gastrulation: Same as chick epiblast Mesoderm and endoderm migrate through primitive streak Migrating cells lose E-cadherin, detach and migrate through Epithelial to mesenchymal transition Migrating cells give rise to notochord Different from chick Notochord becomes integrated into endoderm of primitive gut Converges medially – “buds off” in dorsal direction

Modification for Development with Another Organism 9.26 Amnion structure and cell movements during human gastrulation

Modification for Development with Another Organism FGF (fibroblast growth factors) coordinate cell migration and specification If there is a loss of Fgf8 gene Cell does NOT migrate through primitive streak or forms the other structures later Ectoderm precursors are located anterior to fully extend primitive streak Migrating cells secrete and coat themselves with hyaluronic acid Helps cells separate

Modification for Development with Another Organism Human hypoblast replaced by endoderm Day 14-15 Mesoderm starts forming Day 16

Formation of Extraembryonic Membranes Extraembryonic cells make tissue to allow fetus to survive The trophoblast cells that divides nuclei without cytokinesis Form a layer of synctiotrophoblast Trophoblast cells that divide normal Form a cytotrophoblast

Formation of Extraembryonic Membranes 8.24 Human embryo and placenta after 50 days of gestation Note the sphere to the right is the yolk sac, and chorionic villi extending outward

Formation of Extraembryonic Membranes Cytotrophoblast form and adhere to endometrium Contains proteolytic enzymes Allows them to enter uterine wall Remodel uterine blood vessels Maternal blood bathes fetal blood vessels By secreting paracrine factors – attract maternal blood vessels Syncytiotrophoblast Further the progression of the embryo into uterine wall

Formation of Extraembryonic Membranes Shortly: mesoderm extends outward from gastrulating embryo Called extraembryonic mesoderm Links embryo to trophoblast Becomes umbilical cord Fully developed extraembryonic organ Trophoblast tissue & Mesoderm blood vessels  Called the Chorion

Formation of Extraembryonic Membranes Fuses with uterine wall to create placenta Uterine endometrium (Decidua) – forms maternal side Fetal extraembryonic tissue – forms Chorion Deciduous placenta cannot be separated without damage to both mother and fetus at this stage Villi project from Chorion outer surface

Formation of Extraembryonic Membranes Fetal and maternal circulations never merge (blood cells) 9.27 Relationship of the chorionic villi to the maternal blood supply in the uterus