Lecture 4- Induction of the Nervous System II Flashcards
How was the organizer molecule found?
- the organizer molecule that can induce neural fate found using molecular approaches -cDNA “library” from genes turned on in organizer
- library screened to look for cDNA that could rescue UV treated ventralized frog embryos
How is the cDNA library created?
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What is a UV treated ventralized embryo?
- treat embryo with UV at the right time, no ventral structures form
- can inject cDNA and induce formation of those structures
What are the factors that were identified as neural inducers from organizer? (5)
- first to be identified was Noggin
- then Chordin
- Follistatin
- Cerberus
- Xenopus nodal related 3 (Xnr3)
What is Follistatin and what does it do?
- member of the TGF-beta family
- inhibits Activin
How did Follistatin provide information about how the neural inducers work?
- Follistatin= activin inhibitor
- blocking Activin signalling using non-signalling receptor (dominant negative or DN) induced neural tissue in the animal cap assay
- activin is TGF-beta family member: first evidence that TGF-beta family proteins are epidermalising factors
What are some other TGF-beta (Transforming Growth Factor= TGF) family members apart from Activin?
- Bone Morphogenetic Proteins (BMP’s)
- Nodal
What does the presence of TGF-beta proteins suggest?
- epidermal fate is specified by TGF-beta signalling?
- neural induction involves blocking of TGF-beta signals?
What does the BMP signal transduction pathway look like?
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What does truncated activin receptor do?
-Truncated activin receptor later found to inhibit both activin (which actually works by inducing mesoderm) and BMP signalling
What are the best candidates for native epidermalising factors?
- Bone Morphogenic Proteins (BMPs)
- particularly BMP-2, BMP-4, BMP-7
What happens to dissociated animal cap cells when treated with BMP-4?
- lose their neural fate
- become epidermis
- suggests that if you have BMP signalling you will develop epidermis, thus blocking of BMP signalling leads to neural fate
What does blocking of BMP signalling do?
-induces neural fate
What are the BMP inhibitors and what do they do?
- Noggin, Chordin, Follistatin secreted from the organizer
- block BMP signalling thus inducing neural fate in the neurogenic region
What do Chordin and Noggin bind?
- BMP-4 with high affinity
- blocks BMP-4 from activating receptor
What happens when ectodermal cells are in close proximity to one another?
- BMP signalling inhibits neural fate and the cells become epidermal EXCEPT where they are exposed to organizer signals ( from mesodermal cells that have passed through organizer region- IMZ/DLB during involution)
- the part of the ectoderm above the IMZ is exposed to BMP inhibitors and is induced to become neural and adopts neural fate
What induces neural fate in a chick embryo and how does it happen?
- happens in pregastrular stage
- Fibroblast Growth Factors (FGF’s) induce the neural fate in pregastrular stage in chick embryo
- Fgf3 mRNA is expressed in presumptive neuroectoderm in pregastrula stage
- BMP expression is normally down-regulated in this region
- inhibition of FGF signalling at this stage prevents down-regulation of BMP expression and shifts cells from a neural to epidermal fate (evidence for the FGF’s role in neural induction)
How does FGF inhibition of BMP signalling work? (chick embryo)
- FGF signalling blocks BMP signalling via P-SMAD and via increased Noggin (an FGF target gene)
- inhibits BMP gene transcription
What is the mechanism of repression of BMP in Xenopus? (diagram)
-the mechanism differs in different vertebrate groups
What is the mechanism for repression of BMP signalling in chick embryos?
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