Neural crest and formation of PNS Flashcards
Where do BMPs become restricted to?
BMPs become restricted to region around neural plate
Neural plate border
Develops at the neural – ectoderm boundary
Crucial for:
- Neural crest formation and hence peripheral nervous system development
- Roof plate formation and dorsal neural tube patterning/differentiation
- Final step in neurulation: closure of neural tube
What happens before Shh is expressed, and where is Shh expressed?
Neural crest formation and dorsal neural tube patterning both happen BEFORE Shh is expressed in notochord.
Neural crest formation step one:
An early ‘border’ is established at the interface of the induced neural plate and surface ectoderm. This begins to express specific transcription factors (eg Msx), thought to be induced at ‘intermediate’
levels of BMP signalling.
Neural crest formation step 2
Other signals (Wnts. FGFs, act together with Msx1 to turn on other transcription factors (Pax3, Zic1, Pax7). The combination of these TFs characterises the ‘neural plate border cell’
Neural crest formation step 3
Wnt signals act together with NPB transcription factors (TFs) to upregulate further TFs (c-Myc, Id, Snail etc) that characterise‘neural crest cells’. Note many of these TFs (c-Myc, Id) are TFs that we now know to give cells ‘stem-like’ behaviours: proliferation and multipotency.
Neural crest formation step 4
Ie in reponse to c-myc and Sox9 etc, genes that control proliferation, multipotency and survival are transcriptionally activated
Neural crest formation step 5
At the same time, neural crest cell transcription factors upregulate a further set of genes that promote epithelial-mesenchymal cell transition (EMT). Neural crest cells delaminate from the border region and begin to migrate away
What happens when neural crest cells have migrated out?
Neural tube closes - marks end of neurulation
What do neural crest cells give rise to?
the ‘4th germ layer’: give rise to huge numbers of
different types of cells of the body,
Different cell types generated determined by
(a) position of origin of neural crest cells (determined partly by Hox gene); (b) time of generation of neural crest cells; (c) migratory pathway and the signals they encounter en-route or at target
What do neural plate border cells retained at the border form? what are the important for and what do they express
Roof plate cells.
Roof plate cells are important in the final step of neurulation (forming the neural tube) and in dorsal neural tube patterning.
What do Roof plate cells upregulate?
upregulate BMPs and Wnts.
These secreted signals, diffuse into the dorsal neural tube. They induce expression of a set of transcription factors (Pax6, Pac7, Pax3, Lim1) that cause neural tube progenitors to acquire ‘dorsal identities’
