Figure 1.

Two alternative models to explain NCC diversity: environmental conditioning of multipotent NCC precursors versus specification of NCCs prior to delamination. (A) The “progressive fate restriction model” predicts a hierarchical succession of NCC fate potential from pluripotent (1) via multipotent (2) to bipotent (3) and finally unipotent (4) progenitors. In this model, NCC precursors and some of their immediate progeny are able to self-renew, like stem cells (curved arrow). However, under the influence of signals emanating from cells in their target environment, for example morphogen gradients (indicated in grey), NCCs progressively differentiate into neurons (N), glia (G), melanocytes (M) and myofibroblasts/smooth muscle cells (F). Based on the timing of first NCC emergence and melanocyte differentiation, the events represented in this cartoon should take place between embryonic day (E) 8.5 and 10.5 in the mouse. (B) The “prespecification model” suggests that NCC precursors are fate-restricted before delamination. This model takes into account that neuroglial NCCs exit the neural tube between E9.0 and 10.5 in the mouse and migrate along a ventral path, whereas melanocytes emigrate between E10.5 and 13.5 and migrate dorsolaterally. This model also explains why p75^NTR +ve neuroglial and KIT +ve melanocyte lineages emerge at different times and follow different migratory paths, and why the expression of the NCC guidance receptors NRP1 and NRP2 correlates with NCC fate. Thus, NRP2 is expressed in NCCs contributing to the sensory ganglia, while NRP1 is also expressed in NCCs forming sympathetic ganglia. The stippled arrow indicates that it is not known if NRP1 is expressed in the NCC precursors of chromaffin cells. Note that this cartoon depicts only the intermediate neuroglial and late melanocyte wave, not the early NCC wave. N, neuron; G, glia; M, melanocyte; C, adrenal chromaffin cell.