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

2. 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

3. Cleavage Patterns
5.3 Summary of the main patterns of cleavage

4. Early Mammalian Development

5. 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

6. 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

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

8. 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

9. 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

10. Unique Nature of Mammalian Cleavage
Mammalian blastomeres do not divide at same time
Asynchrony
Do not increase exponentially
( ) 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

11. 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

12. Compaction
9.20 Cleavage of a single mouse embryo in vitro

13. 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

14. Cleavage and Compaction

15. 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

16. 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

17. 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

18. 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

19. Formation of the Blastocyst Cavity

20. Cleavage and Compaction

21. Developmental Potential of the Inner and Outer Cell Masses

22. 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 !!!!

23. 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

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

25. Mammalian Female Reproductive Tract and Early Development

26. 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

27. 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

28. 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

29. 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

30. 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

31. Cleavage and Compaction

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

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

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

35. 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

36. 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

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

38. 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

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

40. 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

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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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