Identification of dividing, determined sensory neuron precursors in the mammalian neural crest

Sensory and autonomic neurons of the vertebrate peripheral nervous system a re derived from the neural crest, Here we use the expression of lineage-spe cific transcription factors as a means to identify neuronal subtypes that d evelop in rat neural crest cultures grown in a defined medium. Sensory neur ons, identified by expression of the POU-domain transcription factor Brn-3. 0, develop from dividing precursors that differentiate within 2 days follow ing emigration from the neural tube. Most of these precursors generate sens ory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants, Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) tr anscription factors neurogenin1, neurogenin2 and neuroD, although it induce s expression of the autonomic-specific bHLH factor MASH1 and the paired hom eodomain factor Phox2a in other cells. These data suggest that there are mi totically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. F urther characterization of the neurons generated from such precursors indic ates that, under these culture conditions, they exhibit a proprioceptive an d/or mechanosensory, hut not nociceptive, phenotype, Such precursors may th erefore correspond to a lineally (Frank, E. and Sanes, J, (1991) Developmen t 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anders on, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differen tiating precursors of large-diameter sensory neurons identified in vivo.