The understanding of cell-cycle control during postnatal neurogenesis has become increasingly interesting with the finding of postnatal stem cells in the adult brain. We have used the olfactory system as a model system for studying the mechanisms involved in postnatal neurogenesis. We have identified several factors that regulate proliferation and differentiation in olfactory receptor neuron (ORN) precursor cells. Two of these factors, which cause proliferation, are members of the neurotrophin family, BDNF and NGF. A third factor, which antagonizes BDNF- and NGF-induced proliferation and promotes maturation of ORNs to the next developmental stage, is a member of the atrial natriuretic peptide family, C-type atrial natriuretic peptide (CNP). This work seeks to further research into the mechanisms of action used by these factors, focusing mostly on BDNF and CNP, to exert their effects on cell-cycle regulation. We will look at their effects as individual factors and also explore the effects of their interactions. We propose to accomplish this through the completion of two broad specific aims.
Aim I is to determine the effects of BDNF and CNP, both alone and together, on levels of various cell-cycle regulatory proteins. We will also seek to determine the role of protein synthesis in regulation of these proteins and determine which of a select set of transcription factors may be involved.
Aim II will focus on unraveling the signal transduction mechanisms used by BDNF and CNP to exert their effects. These experiments should provide valuable information regarding the potential effects of BDNF and CNP in neurogenesis, and also provide more general information on cell-cycle regulation in the postnatal neuron. ? ?
| Simpson, P Jeanette; Moon, Cheil; Kleman, Amy M et al. (2007) Progressive and inhibitory cell cycle proteins act simultaneously to regulate neurotrophin-mediated proliferation and maturation of neuronal precursors. Cell Cycle 6:1077-89 |
