Neural induction Flashcards
Neural induction
BMP antagonists prevent ligand from stimulating its receptor
Cell differentiation
Process by which cells become different from each other and acquire specialized properties. Governed by changes in gene expression, which dictate the repertoire of protein synthesized.
Gene expression in a cell can be governed by
extrinsic factors (eg morphogens) and intrinsic factors (eg transcription factors)
Dpp/Sog dictate?
dorsal and ventral sides of inects/worms
How does neurogenic region in invertebrates form?How the does neural plate in vertebrates form?
where dpp is inhibited by BMP antagonist Sog, the neurogenic region forms
where the BMP antagonist chordin inhibits BMPs
Homologs in vertebrates and invertrbrates
Xenopus:Drosophila BMP7:Screw BMP1:Tolloid BMP4:Dpp Chordin: Sog (short gastrulation)
Fates of ectoderm with BMP and ectoderm with no BMP signalling
BMP - Epidermal differentiatiion
No BMP - Neural differentiation (neural ectoderm)
Cells in mesoderm
Organizer cells (spearman organiser) express TF’s (Gsc) which binds to enhancer and intrinsically transcriptionally activate genes that encode BMP antagonists (Chordin, noggin, follistatin). Once translated – diffuse into ectoderm and inhibit BMP signals/signalling.
Ventral centre in mesoderm express - BMP4, tolliod, Tsg
Stages of mesoderm induction
and patterning:
- Low level Nodal gives ventral mesoderm
- High level Nodal gives organiser
- 3.Signals (chordin, Noggin etc) from organiser act to inhibit BMPS- to ‘dorsalise’ and pattern the adjacent (ventral) mesoderm
- At same time, antagonism of BMPs in ectoderm lead tissue to acquire neural identity
Node in Chicks and humans:
A specialised mesoderm region, called the Node.
Secretes BMP antagonists, which induce the neural plate
Upregulating Sox2, changing fate and producing neural plate
Organiser = Node
In Situ hybridization
it involves the hybridization of a labeled RNA or single-stranded DNA probe with a specific target nucleic acid (RNA or genomic DNA) within a cell.
What happens when neural plate/organiser is induced?
Dorsal mesoderm involutes and undergoes convergent extension (to lie underneath the ectodermal, or top, layer of the embryo). As it does so, it self-differentiates into notochord (most of it) and prechordal mesoderm (right at front).
Neural plate lengthens to form neural tube.
The two conclusions made from neural induction in Xenopus - the organiser graft experiment
The secondary neural tube was host-derived - ie showing that the neural tissue is induced from the ectoderm, in response to signal(s) from the organiser tissue.
The axial mesoderm (prechordal mesoderm and notcohord) and anterior endoderm were donor-derived showing that they had self-differentiated from the origaniser
Types of experiments performed to prove that BMP antagonists are secreted from the organizer and induce neural plate
- Genes for BMP antagonists expressed in organiser
- BMP antagonists are secreted and act on adjacent cells
- Overexpression of BMP antagonists in an ectopic site lead to induction of secondary axis
- Inhibition of activity (eg via knock-out or injection of a dominant negative effector of the signalling pathway) prevents axis formation
How were BMP antagonists discovered?
Discovered BMP antagonists by extracting ALL mRNA from organiser cells, reverse transcribing to cDNA, then testing each to look for a gene/protein that would mimic the organiser’s ability to induce a secondary neural plate