trkC-mediated NT-3 signaling is required for the early development of a subpopulation of neurogenic neural crest cells.

Soon after they segregate from the neural tube, trunk neural crest cells disperse on two spatially and temporally distinct pathways. Only crest cells that migrate early and ventromedially give rise to neurons of the peripheral nervous system. It is also known that neural crest cell-derived populations require appropriate environmental cues early in development in order to generate neurons, and for the subsequent survival of differentiated neurons. We examined whether neurotrophin-3 (NT-3), a survival factor for subsets of peripheral neurons, is also involved in the regulation of neurogenesis by neural crest cells. First, we found that premigratory and migrating neural crest cells on the medial migration pathway of Embryonic Day 2.5 (E 2.5) embryos express mRNAs encoding multiple isoforms of the NT-3 receptor, trkC, as do cells in the neural tube and epithelial dermamyotome. On E4, a subpopulation of neurons in nascent sensory ganglia express trkC message. Second, we demonstrate that trkC mRNA is only expressed in neural crest cell populations that possess neurogenic potential. Third, we show that the presence of NT-3, during the initial development of cultured neural crest cells, is required for neurogenesis by a subpopulation of neurogenic neural crest-derived cells. These results suggest that a subpopulation of neurogenic neural crest cells expresses functional trkC receptors and requires the timely availability of NT-3 for their development before reaching their final embryonic locations. We suggest that developmental heterogeneity exists in the identity and requirements of neural crest cell subsets that harbor neurogenic potential. We also suggest that the "paradoxical" expression of trkC receptors by the somitic dermamyotome may, in fact, play a role in the exclusive development of crest-derived neurogenic precursors on the medial pathway by limiting the availability of NT-3 on the lateral pathway.