Gastrulation – The reorganisation of the embryo from a single layer of cells to multiple layers.
Embryos may survive without functional gastrulation but they will be born with morphological
defects like in caudal dysplasia.
0-6 days of human development
1. Fertilisation occurs roughly 12-24 hours after ovulation. This is the point where DZ twins are
possible if 2 eggs are released during ovulation, and both are fertilised.
2. The male pronuclei provide the first mitotic spindles to reach the 2-cell stage at roughly 6
hours after fertilisation. The 2 and 4 cell stage is where formation of MZ twins is most likely
3. ~3 days after fertilisation you have a morula containing 12-16 blastomeres. The morula is
the first point at which not all cells are identical – this happens at the 16-cell stage when
you get differential gene expression.
4. ~4 days an advanced morula reaches the uterus.
5. ~12-24 hours later the zona pellucida is cleaved off and leaves behind an early blastocyst
which begins to implant into the endometrium at roughly 6 days post fertilisation. The
blastocyst is the first point where there are multiple cell types.
Formation of Inner and Outer Cell Mass
At the 8-cell stage inner cells begins to segregate from the outer cells.
The ICM (dark grey) develops into an embryo and the OCM (light grey) develops into the trophoblast
which later develops into the placenta.
Once the ZP gets cleaved off we are left with a blastocyst. In a blastocyst there is a clear
differentiation in gene expression between the ICM and the OCM/ trophoblasts. The OCM begins to
pump in fluid to form a blastocyst cavity at 4.5 days. The trophoblast cells begin to differentiate into
different cell types to help implantation at ~6 days.
, ICM differentiation
The ICM becomes the Epiblast and hypoblast – these become the amniotic cavity and the yolk sac
respectively.
OCM differentiation
The trophoblasts differentiate into the syncytiotrophoblasts (SCT) and the cytotrophoblast. (CT)
SCT forms an epithelial layer without intercellular boundaries meaning they have direct contact with
maternal blood. They form cords that infiltrate into the endometrium. Apoptosis of endometrial
stromal cells creates spaces that allows the blastocyst to penetrate deeper into the endometrium.
They are fully differentiated trophoblasts.
CT consist of an irregular layer of ovoid. They are mononucleated cells which sit under the SC and
are undifferentiated, essentially making them the ‘SCT stem cells’. They are important for
connection with the spiral arteries, improper cytotrophoblast invasion may be linked to pre-
eclampsia.
15 days
Up to 15 days the embryo is one cell thick. At 15 days the primitive streak and primitive node begin
to appear in the epiblast. This indicates the initiation of gastrulation and is thought to be the most
important part.
The primitive streak cells produce FGF8 which controls cell migration and specification. FGF 8
controls cell movement by downregulating E-cadherin, detaching the epiblasts from each other.
The movement of the epiblast cells towards to primitive streak causes them to interact with FGF8,
detach and slip beneath the epiblast. The first cells to move inwards displace the hypoblast and
create the definitive endoderm.
Some cells interact with the FGF8 in the mesoderm. FGF8 regulates brachyury (T gene) expression,
which switches these cells on to become the definitive mesoderm.
Those cells that stay and don’t interact with the primitive streak become the ectoderm.