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CREB-dependent mechanisms regulating neural stem/progenitor cell proliferation and neurogenesis

Objective

Amongst the many factors regulating neural stem and progenitor cell (NSPC) proliferation, survival and differentiation, transcription factors are important factors governing gene expression in NSPCs. Several recent reports indicate that the prototypical transcription factor, cyclic-AMP Element Binding protein (CREB) displays restricted constitutively activated expression in mouse brain neurogenic zones. Germline and conditional panneuronal-specific inactivation of the Creb1 gene has shown the critical role CREB plays in neuronal survival. Closer examination of these mutant mouse brains also indicates significantly reduced cerebral size, implying CREB has a role in neurogenesis, independent of neuronal loss. Our most recent studies have made some progress toward deciphering the role of CREB in NSPCs using zebrafish as a model, where we found that we could modulate neurogenesis by modulating CREB activity. However, knowledge of the role of CREB in mammalian NSPC function is still at an early stage. Using state-of-the-art molecular genetic techniques and bioinformatics approaches, this proposal aims to thoroughly investigate the role of CREB in mammalian NSPCs in vitro and in vivo, during both mouse development and in the adult mouse brain. The study will also investigate whether CREB also has a role in the development and growth of brain tumors. Since CREB is widely expressed and many of the molecular networks between NSPCs and other stem cell types are shared, I anticipate the data obtained from this project will be applicable, not only to neural stem cells but to many other tissue-specific stem cells.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /natural sciences/biological sciences/molecular biology/molecular genetics

Call for proposal

FP7-PEOPLE-IRG-2008
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

PANEPISTIMIO PATRON
Address
University Campus Rio Patras
265 04 Rio Patras
Greece
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Eleni Lekka (Ms.)