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The role of CREB in neurogenesis, cell proliferation and brain organization| old_uid | 3175 |
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| title | The role of CREB in neurogenesis, cell proliferation and brain organization |
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| start_date | 2007/09/17 |
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| schedule | 12h |
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| online | no |
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| details | invité par François Tronche |
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| summary | The characterisation of genes which regulate neural homeostasis is crucial to identifying the signalling pathways involved in disease; both during embryonic development and in adulthood. The highly conserved cAMP Response Element Binding protein (CREB), is a transcription factor which has well-characterized roles in neuronal activation and survival, mechanisms of addiction and memory potentiation, although a role for CREB in early development and neural stem/progenitor cell (NSPC) proliferation has not yet been described.
Using the zebrafish as a model, we have characterised the localisation of activated CREB (pCREB) in the adult zebrafish brain, and find that pCREB localises to all known proliferative and neurogenic regions, including for the first time, actively proliferating cells. By injecting mRNA encoding dominant-negative or constitutively active CREB RNA into zebrafish embryos, we show that CREB regulates midbrain-hindbrain organization, somite morphology and NSPC proliferation.
Mice lacking CREB display defects in brain organisation, proliferation and cellularity. Cultured murine NSPCs from these mice show defects in neurosphere formation, self-renewal, survival and proliferation. The expression of several well-characterised CREB target genes is reduced in CREB-/- neurospheres. Taken together, these data indicate a role for CREB in neural development and NSPC proliferation. |
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| responsibles | Francheteau |
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