The factors that mediate glial formation by neural crest progenitors that form the peripheral nervous system (PNS) are not well understood. Notch signaling can mediate gliogenesis in cultured neural crest progenitors. However, the gliogenic effect of Notch activity in vitro could depend on additive signals in the culture environment that may not be physiologically relevant. The question of whether Notch regulates gliogenesis in the developing PNS can be addressed in three parts. First, is Notch signaling necessary for gliogenesis in the developing PNS? Second, is Notch signaling sufficient for gliogenesis in the developing PNS? Third, what are the molecular signals that mediate Notch-dependent gliogenesis in cultured neural crest progenitors? To answer these questions, transgenic rodent models will be used to selectively disrupt or constitutively activate Notch signaling in neural crest progenitors. Also, rat neural crest progenitors will be isolated to test whether expression of selected downstream mediators of Notch signaling is sufficient to promote gliogenesis. These approaches will address whether Notch signaling positively regulates gliogenesis in the developing PNS by addressing both the physiological relevance and mechanisms of Notch-mediated gliogenesis in neural crest progenitors.
