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The nervous system consists of many different types of neuron. How are all these types formed, and how do their axons establish specific, functional circuits? These fundamental questions remain largely unanswered. Cell fate decisions and phenotypic differentiation are governed by signalling from local organizing centres. This signalling regulates intrinsic transcriptional programmes that, in concert, direct cell fate commitment.
The multipotent trunk neural crest can generate many types of cell, including sensory, sympathetic and enteric neurons of the PNS (FIG. 1a,b). The neural
crest is both technically and conceptually an attractive model system in which to investigate how neuronal diversity is created. Under strict spatiotemporal control by signals from the neural tube, neural crest cells (NCCs) delaminate from the neural tube and some migrate ventrally between the dermamyotome and the neural tube to generate the dorsal root ganglia (DRG)1.
During migration and upon condensation into a ganglion, NCCs are exposed both spatially and temporally to signals from the adjacent somites and spinal cord, which drive the generation of multiple types of sensory neuron in the DRG (FIG. 1b,c). These neurons
enable us to sense touch, warm, cold, pain, limb movements and limb spatial position.
Different types of DRG neuron are specialized for the different perceptual modalities. Each functional type of sensory neuron has unique molecular characteristics, contains unique sets of ion channels and responds to unique sets of stimuli. Such types include small diameter
neurons with thinly myelinated or unmyelinated axons that either contain or do not contain neuropeptides (such as neurotrophic tyrosine receptor kinase A-containing (TrkA+) peptidergic and TrkA non-peptidergic neurons), most of which respond to noxious stimuli (nociceptive neurons) and mediate pain sensations, larger diameter low threshold mechanoreceptive neurons conveying mechanical sensations (for example, touch; these include TrkB+ and/or TrkC+ neurons) and large proprioceptive neurons that sense limb movement and position (TrkC+ neurons). Sensory neurons have stereotypical terminations that generate highly reproducible patterns of connectivity in the spinal cord. The experience of different perceptions depends on where the sensory neurons terminate in the spinal cord (FIG. 1c).
The development of the molecular characteristics and receptive properties of sensory neurons must therefore be tightly linked to their central terminations. These properties of sensory neurons make them particularly attractive for studying how neuronal subtypes are...