CREB activity modulates neural cell proliferation, midbrain-hindbrain organization and patterning in zebrafish
- Dworkin, S., Heath, J.K., Dejong-Curtain, T.A., Hogan, B.M., Lieschke, G.J., Malaterre, J., Ramsay, R.G., and Mantamadiotis, T.
- Developmental Biology 307(1): 127-141 (Journal)
- Registered Authors
- de Jong-Curtain, Tanya A., Heath, Joan K., Hogan, Ben M., Lieschke, Graham J.
- CREB, Neurogenesis, Midbrain–hindbrain boundary, Zebrafish
- MeSH Terms
- Body Patterning*
- Cell Proliferation*
- Central Nervous System/growth & development
- Cyclic AMP Response Element-Binding Protein/physiology*
- 17531969 Full text @ Dev. Biol.
Dworkin, S., Heath, J.K., Dejong-Curtain, T.A., Hogan, B.M., Lieschke, G.J., Malaterre, J., Ramsay, R.G., and Mantamadiotis, T. (2007) CREB activity modulates neural cell proliferation, midbrain-hindbrain organization and patterning in zebrafish. Developmental Biology. 307(1):127-141.
Neural stem/progenitor cells (NPCs) self-renew and differentiate, generating neuronal and non-neuronal (glial) cell lineages. Although a number of factors, including transcription factors, have been shown to be important in the regulation of NPC proliferation and differentiation, the precise molecular networks remain to be identified. The cAMP Response Element-Binding protein (CREB) is a transcription factor important for neuronal survival, differentiation and plasticity. Recent work suggests that CREB activation, via serine phosphorylation in the kinase inducible domain, is important for neurogenesis in the adult rodent brain. We sought to further investigate CREB function in neurogenesis, using the zebrafish (Danio rerio). Structural and functional analysis of the zebrafish CREB orthologue showed high conservation with mammalian CREB. Activated (phosphorylated) CREB (pCREB) was localised to all known proliferation zones in the adult zebrafish brain, including actively cycling cells. Furthermore, we found that modulating CREB activity during early zebrafish development caused significant defects in neural proliferation, midbrain-hindbrain organization and body patterning. These findings reveal broader and stage-specific physiological roles of CREB function during vertebrate neural development and proliferation.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes