Lecture 8 Germ layer induction and gastrulation
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What do morphogens induce and how?
• Morphogens induce different transcriptional profiles, in a concentration dependent way
How is cell fate determined
Through extrinsic and intrinsic factors
How does development occur
Through a combination of cell proliferation, differentiation, migration and tissue morphogenesis
Define morula
A uniform group of cells
When do most miscarriages occur?
In the 1st 12 weeks due to failed germ layer formation/gastrulation
What is the first step in germ layer formation/gastrulation
Set aside ‘top’ cells versus ‘bottom’ cells by differentiation
How does the first step in gastrulation occur x3
• Different cytoplasmic determinants i.e. heavy components in the cytoplasm of the original cell ‘sink’ to the bottom under the effect of gravity (in mammals, one side of the embryo implants into the uterine wall to define the direction i.e. due to interaction with the placenta). • Initiate early differences in future bottom (vegetal hemisphere) versus top (animal hemisphere) cells • Oocyte (egg) is already polarised, even before fertilisation. Particular cell components are specifically found in the ‘vegetal hemisphere’
Do the top or bottom cells differentiate into the 3 germ layers and why?
The top cells The bottom cells signal to the top cells to differentiate further forming 3 germ layers
What occurs in the 3rd division of the morula What is the important thing here
Horizontal cleavage 4 cells on top and 4 on bottom Gives animal and vegetal cells Important thing is breaking symmetry
What is the second step in germ layer formation
A blastocoel (hole) forms in the animal hemisphere due to changes in cell adhesion and polarity. This is known as a blastula
Which hemisphere do the germ layers come from
The germ layers all come form the animal hemisphere = non Vg1-expressing part
How do the 3 germ layers arise from the animal hemisphere?
Mesoderm induction VgT TF family is localised to V hemisphere cell nuclei and binds to the promotor of and activates transcription of the gene Nodal
How do we know VgT is expressed vegetally
In situ hybridisation - make antisense probes to see if particular gene is transcribed in a particular cell to give a white dot
What does VgT code for
A secreted morphogen i.e. Nodal
What occurs when Nodal is translated
It diffuses out of vegetal cells into animal cells which contain R for it to activate the Nodal signal transduction pathway
What is the result of activation of nodal
cause that cell to change its behaviour (cell proliferation/migration/differentiation).
In cells seeing high levels of Nodal, what do they differentiate into
Endoderm
In cells seeing mid levels of Nodal, what do they differentiate into
Mesoderm
In cells where the Nodal signalling pathway is not activated what do cells differentiate into
Ectoderm
Why is the vegetal hemisphere so important
It signals to animal hemisphere to induce mesoderm and endoderm, otherwise animal hemisphere would just form ectoderm Explains how 3 germ layers form
What does VgT signalling not explain
How a particular part of the embryo arises that will drive gastrulation and axis formation
Explain DV axis formation
• Dorsalising factors sink to the vegetal pole • Sperm fertilisation only on animal side • Causes a 30 degrees cortical rotation • Dorsalising factors shift to a new position • Dorsalising factors activate Wnt sig pathway • This marks future dorsal/posterior part of the body and is the site where gastrulation is intiated • Beta-catenin enter the nucleus to act as a TF • In the Nieuwkoop centre, VgT and beta-catenin overlap • Co-expression of β-catenin and VgT turns on Nodal at very high levels. The mesoderm and endoderm, induced in response to Nodal signalling, at this point is slightly different: it’s Spemann’s organiser (cells receiving Wnt and very high Nodal).
What is the organiser called in humans/chicks
Node or Hensen’s node
Why does this combination of high Nodal and active Wnt induce the organiser? ie cells with a particular transcriptional signature?
A proximal element to the goosecoid (Gsc) gene is bound by β-catenin and Wnt; a distal element is bound by TGF-β/Nodal. Genes like goosecoid (Gsc) are only transcriptionally activated via BOTH a Nodal downstream effector (Smad2/4) and a Wnt/beta catenin downstream effector.