Chapter 5: Gastrulation
Introduction to the process of gastrulation
Gastrulation is responsible for embryo organization → during this process some of the
embryonic ectoderm will transform into mesoderm & endoderm (and the mesoderm
will differentiate into subtypes of mesoderm) → this is the exact moment the embryo
exists out of 3 germ layers.
When does gastrulation happen in the development of the embryo?
- Fertilization
- Cells start to cleave → formation of the blastula (= hallow ball with a clump of
cells) → embryo consists of 2 germ layers → endoderm & ectoderm.
- Gastrulation happens → formation of the gastrula → cells start to migrate & form
the third germ layer → mesoderm.
Together with gastrulation and the formation of mesoderm, we also have the formation of
the body axis & a primitive body plan.
Cells are given new positions & neighbors Gastrulation results in the formation of:
(migration – cells come in contact with different - Ectoderm
cells and other signaling molecules) & this is - Mesoderm
combined with the transformation of epithelial - Endoderm
cells into mesenchymal cells (EMT) and
endoderm cells. + formation of body axis, …
- Folding happens → neurulation (formation of the nervous system) →
gastrointestinal track starts to form.
- Organogenesis makes the organs start to develop.
Phylotypic stage
Across all different organisms, there is a moment/stage in their development where they
all look alike → we compare them all to study gastrulation.
The other stages (like cleavage, organogenesis, …) are different between the species.
,→ Gastrulation stops when the organism gets the form of a shrimp.
The 3 embryonic germ layers
Every single cell in our body is derived from one of these layers.
Ectoderm (outside) - Epidermis
→ apical-basal polarity + columnar cells - Nervous system
- Neural crest cells
Mesoderm (the middle) - Skeleto-muscular system
→ loose + apolar cells - Connective tissue
- Blood/cardiovascular system
- Urogenital system
Endoderm (inside) - Gastro-intestinal system &
→ thight + flattened cells associated organs (lungs, liver,
pancreas, …)
- Formation of a primitive gut
(archenteron)
When the three germ layers first form during gastrulation, all 3 are primarily made
of epithelial cells:
• Tightly connected with adhesive cell junctions
• Organized in sheets
• Polarized (top and bottom side → the bottom is attached to a membrane by
integrins).
The mesoderm undergoes an epithelial-to-mesenchymal transition (EMT):
• Epithelial cells lose tight connections
, • They become mesenchymal cells (loose & migratory cells)
Epithelial-to-mesenchymal transition (EMT) & MET
Ecto-, endo- & mesoderm are first made up of epithelial cells → EMT is the process of
transforming these epithelial cells into mesenchym cells to further distinguish the
mesoderm → this happens during the activation of gastrulation in specific places of the
embryo.
- Starts with an epithelial layer of ectoderm → settled on a basal lamina.
- The epithelial cells are connected to the lamina with integrins + the cells are
connected to each other with E-cadherin, Actin, Catenins, …
= apical-basal polarity
- Paracriene factors are released → changes in transcriptomes of the cells →
triggers the formation of mesenchymal cells → cell adhesions are broken & the
basal lamina gets dissolved.
- Mesenchymal cells escape the basal lamina & can start to migrate (→
reorganization of the cytoskeleton → cells can operate as individual units).
Triggers for EMT
• Transcription factors that trigger EMT:
o ZEB-family (ZEB1/2)
o SNAIL and/or SLUG
o TWIST1
• TF are ACTIVE → repression of epithelial genes (E-cadherin, Occludines,
Claudines, …) & activation of mesenchymal genes (N-cadherin, Vimentin,
Fibronectin, …).
= cells become migratory mesenchymal cells
• TF are INACTIVE → epithelial genes remain expressed & cell junctions remain
intact.
= cells stay epithelial
, Cells don’t always switch fully → they often go through partial EMT (= they have both
epithelial and mesenchymal features. This happens in:
• Embryonic development
• Wound healing
• Cancer metastasis
Triggers for MET
• Loss of EMT-inducing signals (EMT is mostly triggered by pathways like Notch,
Wnt, …) → when these are turned off, epitelial genes are no longer inhibited.
• Activation of epithelial gene programs to restore tight junctions, cell-cell
adhesion, …