Significant evidence suggests that stem cells are present in diverse peripheral locations within the nervous system. Bone morphogenetic proteins have been shown to promote neurogenesis in these multipotent populations, although the timing and selectivity with which uncommited, non-neuronal cells are promoted to undergo neurogenesis remains unclear. This proposal will identify the role of BMPs in cell fate specification using both in-vitro cell culture techniques and an in-vivo, inducible knock-out model. Evidence indicates that increases in neurogenic potential are paralleled by an inhibition of alternative cell fates. We will directly test the hypothesis that BMPs increase neurogenesis by limiting or preventing glial differentiation. This investigation will be carried out in sympathetic and enteric precursor populations, and will identify the effects of BMPs on these progenitors during embryonic development. By understanding the extent to which peripheral nerve cells retain plasticity in developmental potential, we can begin to address therapeutically, a wide range of pathologies including nerve injury as well as de-myelination disorders typified by Charcot-Marie-Tooth Syndrome and HNPP. Additionally, we will better describe the key regulators of lineage specification during nervous system development.
| Dore, Justin J; DeWitt, John C; Setty, Nithya et al. (2009) Multiple signaling pathways converge to regulate bone-morphogenetic-protein-dependent glial gene expression. Dev Neurosci 31:473-86 |
| Dore, Justin J; Crotty, Kate L; Birren, Susan J (2005) Inhibition of glial maturation by bone morphogenetic protein 2 in a neural crest-derived cell line. Dev Neurosci 27:37-48 |
