ZFIN ID: ZDB-PUB-070614-18
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.
Date: 2007
Source: Developmental Biology   307(1): 127-141 (Journal)
Registered Authors: de Jong-Curtain, Tanya A., Heath, Joan K., Hogan, Ben M., Lieschke, Graham J.
Keywords: CREB, Neurogenesis, Midbrain–hindbrain boundary, Zebrafish
MeSH Terms:
  • Animals
  • Body Patterning*
  • Cell Proliferation*
  • Central Nervous System/growth & development
  • Cyclic AMP Response Element-Binding Protein/physiology*
  • Mesencephalon/physiology*
  • Neurons/cytology*
  • Phosphorylation
  • Rhombencephalon/physiology*
  • Zebrafish
PubMed: 17531969 Full text @ Dev. Biol.
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.