11 - Gastrulation and development of the embryonic germ layers

What does polarisation of the epiblast do

Cells develop lateral, apical and basal domains

Formation of pro-amniotic cavity

Cells on apical surface undergo programmed cell death

Debris phagocytosed by ectoderm cells

Cavity created

Anterior visceral endoderm (AVE)

Specialised region of the VE

Mechanism of the AVE

Patterning in early embryo

AVE move unidirectionally from it’s initial position at the distal tip of egg cylinder to the future anterior of the embryo

What TF does AVE express

LIM-1

What is LIM-1 required for

Head formation

Where are the 3 embryonic germ layers established

Ectoderm, mesoderm, endoderm

Cadherins

Regulate cell adhesion and important role in regulating cell movements during development

Transmembrane proteins

Extracellular domain can bind to another cadherin of the same type

Binding is calcium-dependent

Intracellular domain binds to cytoskeleton (requires Beta-catenin)

How does Beta-catenin respond to pressure

Translocates to the nucleus and turns on key genes required for invagination

Twist gene

TF required for invagination

What does the twist gene turn on

Mesodermal genes that are required for heart and muscle development

TF snail

Turns off genes for neuronal development

Mechanism of the nuclear translocation of Beta-catenin

Causes cadherin-cadherin interactions to be destabilised

Cadherins no longer attached to the cytoskeleton

Enables the cells to move freely

What can factors released by AVE supress

Gastrulation

Delamination

Loosening of primitive endoderm during gastrulation so it can move through the primitive streak

What do ectoderm cells at the primitive streak undergo

Epithelial to mesenchymal transition

What is needed for epithelial to mesenchymal transition

Reduced E-cadherin levels in the epithelial

Brachyury

TF for differentiation of mesoderm

How are E-cadherin levels reduced

FGFR binding

Dimerisation and autophosphorylation of tyrosine residues on intracellular domain

Initiates downstream signalling cascades

What happens if Brachyury is not expressed (homozygous mutant)

Defected mesoderm formation

No trunk and tail

Die around embryo day 10

Brachyury +/- mouse (heterozygote)

Shortened tail

Abnormal sacral vertebrae

What can cause incorrect gastrulation in humans

Genetic abnormalities

Toxic insults

What features does mesoderm contribute to the formation of

Lower limbs

Urogenital system

Vertebrae

What defects occur from mesodermal abnormalities

Hypoplasia

Lower limb fusion

Vertebral abnormalities

Renal agenesis

Genital organ abnormalities