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.
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