DB2 MARVELLOUS MAMMALIAN DEVELOPMENT

Unique features in mammalian development

Slow cell division

Limited maternal factors

Rotational and asynchronous cleavage

Cellds end up in one of two microenvironments that determine cellular fate - embryonic or placental fate

Morula

3 - 4 days post-fertilisation

Loosely packed ball of cells

Blastocyst

4 ½ - 5 days post-fertilisation

Mammalian embryo

Needs to establish an interaction with the maternal blood supply to provide the factors required for its further development

Development of an adequate placenta is crucial to embryo survival and development

Compaction

Between day 3 and 5

Cells flattening against each other by increasing cell-cell adhesion through E-cadherin forming first permeability barrier

E-cadherin

Forms tight junctions which establishes polarity across the epithelium

Differentiation at 32 cell stage

Trophoblast cells → Future placenta

Inner cell → Fetus

Cavitation

Na⁺ ions move across apical membrane → Na⁺/K⁺ ATPases pump Na⁺ across basolateral membrane causing Na⁺ ions to accumulate in blastocyst and increase osmotic pressure → Cl^-/HCO₃^- exchangers maintain electroneutrality → Osmotic pressure causes water to build up and expand the blastocyst cavity

Same number of cells but larger blastocoel volume

Radial cleavage

Expansion of trophoblast layer making more cells with the same cell volume

Generation of more trophoblast cells along the horizontal plane

Tangential cleavage

Generation of more cells in the inner cell mass along the vertical plane

Fate distribution

Dependent on position of cells in the morula, outer → trophoblast, inner → inner cell mass

Too few cells in morula → all trophoblast cells → trophoblastic vesicle and no embryo develops

Between 16 and 64 cell stage the fates are fixed

Chimeric blastocyst

Aggregation of early embryos produces a large blastocyst and one fetus

Demonstrated that cells were totipotent at 8-cell and 16-cell stage

Cells are committed to lineage by 64-cell stage

Implantation

Trophoblast cells adhere to uterine epithelium and their invasive properties allow the embryo to implant within the endometrium

Further cell lineages are established by positional information and cell-cell interactions

In vitro fertilisation

Early cleavage embryos transferred into the oviduct (invasive, painful, and less successful)

Blastocysts transferred through the uterus (less invasive and more painful)

Embryo screening

X-linked diseases, cystic fibrosis, Down’s syndrome