10 - Early stages of mammalian development

Cleavage

Cell division without cell growth

Role of Zone pellucida

Prevention of embryo implanting prematurely in the fallopian

Premature implantation of embryo in fallopian tube

Ectopic pregnancy

Formation of monozygotic (identical) twins

Embryo splits during cleavage

Why would a blastomere be removed from the embryo

For preimplantation diagnosis

What do blastomeres do at compaction

Maximise cell to cell contact to form morula

What molecule does compaction require

E-cadherin

What does E-cadherin depend on

Calcium

When does the first differentiation occur

After compaction

In the first differentiation, what do the surface cells turn to

Trophectoderm cells

Oct4

Required for development of inner cells and for the pluripotency of ESCs

Cdx2

Required for trophectoderm

Switches off Oct4

What happens if Cdx2 is blocked

Trophectoderm does not develop and the blastocyst does not form

Embryo death

Functions of the trophectoderm

Pump Na+ ions into morula

Hatching from zona pellucida

Maintenance of pregnancy

Formation of placenta

Trophectoderm as Na+ pump

Pumps Na+ ions inside the morula to form blastocyst

Water follows through osmosis

What prevents the blastocyst from expanding too much

Zona pellucida

What side of cells is E-cadherin expressed on

Lateral side

Cell polarity

Intrinsic asymmetry

Where do epithelial cells like trophectoderm become polarised

Along the apical basis axis

What does polarisation along apical basis axis cause

Different protein consumption at apical and basal surfaces

Polar trophectoderm cells location

In direct contact with the underlying epiblast

Mural trophectoderm cells location

Line the blastocoel cavity

What is mural trophectoderm required for

Hatching from zona

Give rise to trophoblast giant cells

Mechanism of mural trophectoderm in hatching from zona

Strypsin secretion

Lyses a hole in the zona

Blastocyst to escape

Trophoblast giant cells

Terminally differentiated

Non-invasive (don’t help with embryo implantation)

What does polar trophectoderm differentiate into

Highly proliferating cytotrophoblastic cells

What forms when nuclei of cytotrophoblastic cells divide too fast and cells fuse

Synctiotrophoblastic cells form

What is the syncytium responsible for

Implantation of the embryo within the uterine wall

What is in the inner cell mass of mature blastocyst

ESCs

Primitive endoderm (hypoblast)

Function of primitive endoderm

Deposit basement membrane at basal surface

Give rise to some extraembryonic tissue

Secretion of signalling molecules

What does FGF stand for

Fibroblast growth factor

FGFs

Role in development

Secreted from and bind to the same cell or another cell type

What does primitive endoderm differentiation depend on

FGF binding to FGFRs on the surface of primitive endoderm cells

Mechanism of FGF signalling in surface cell differentiation

Binding to FGFRs

Expression of TF Gata6

Suppression of Oct4 and other pluripotency genes

Turns on genes that are needed to make basement membranes eg. collagen and laminin

Oct4

Transcription factor requires to prevent premature differentiation of ESCs and maintain pluripotency

GATA6

Transcription factor required for differentiation of primitive endoderm

What makes up the primitive endoderm

Parietal and visceral endoderm

Why does parietal endoderm have extensive RER

To excrete lots of extracellular membrane proteins

Function of parietal membrane

Secrete extracellular membrane proteins which are incorporated into a specialised basement membrane called Reichert’s membrane

Role of Reichert’s membrane

Prevents maternal cells entering parietal yolk sac and destroying the embryo

Lack of Reichert’s membrane

Embryo death

Key molecule in parietal endoderm differentiation

PTHrP - parathyroid hormone related peptide

What expresses PTHrP

TE

NOT by ESCs

Function of visceral endoderm

Nutrients for embryo

Supports growth before placenta development

Secretes signalling molecules

What drives visceral endoderm differentiation

Factors derived from the ESCs / epiblast cells

BMPs

Pseudostratified epithelium

Appears multiple layered due to the way the nuclei lay but is actually single layer

What induces polarisation of the epiblast

Signals from the basement membrane