Cell lineage determination and the control of neuronal identity in the neural crest

Abstract

The molecular mechanisms underlying the determination of neuronal identity in the vertebrate peripheral nervous system are only just beginning to come into focus. Many of these mechanisms, such as the involvement of cascades of bHLH transcription factors and lateral inhibition via the Notch-Delta system, appear to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993). The way in which these genetic circuits are controlled by instructive growth factors, and the manner in which they lead to expression of a particular neuronal identity, is far from clear. This process is being elucidated by studies of neurogenesis in the peripheral autonomic lineage, which is arguably the best-understood neurogenic lineage in vertebrates. Emerging evidence is beginning to suggest that neuronal diversity within the autonomic and sensory lineages may be generated by related, but distinct, mechanisms. All autonomic progenitors express a common bHLH protein, MASH1, which appears to be induced by members of the BMP2 subfamily secreted by the tissues to which these progenitors migrate. Additional signals may then act on these progenitors in different locations to induce the expression of other transcription factors, which act in conjunction with MASH1 to specify the final phenotypes of the different autonomic neuron subtypes (sympathetic, parasympathetic, and enteric). Although different classes of autonomic neurons develop in very different locations within the body, different classes of sensory neurons are located together in dorsal root ganglia. The finding that distinct but related subtypes of bHLH proteins, the neurogenins, are expressed by different classes of sensory neuron precursors early in development suggests that sensory neuron diversity, in contrast to autonomic neuron diversity, may be pre-specified at or before the time neural crest cells begin their emigration from the neural tube.