9 – 11 In addition, timing, or an intrinsic developmental clock, plays a key role in determining the types of progeny that are generated, resulting in a stereotyped sequence in which retinal ganglion cells are the first cell type generated and Muller glia cells are the last. 8 As in the case of the neural crest, multiple environmental cues have been shown to alter cell fate, yet evidence also exists for lineage-restricted subsets of precursor cells. In many respects, the mechanisms mediating fate determination of NCCs may be analogous to those that drive the fate of cells in the vertebrate retina. 3 – 6 Back-transplantation studies are consistent with the idea that although phenotypically distinct precursor cells may be prespecified, many of them are not committed and their fate and/or those of their progeny can be determined by cues in their local environment. Although considerable transplantation evidence supports the first thesis, 2 lineage-tracing studies provide evidence for the presence of both restricted subpopulations of precursor cells and multipotent stem cells whose fates can be altered by local environmental cues. These data provide evidence for the fate prespecification of subsets of NCCs while still resident in the neural tube.Ī fundamental question in developmental biology is whether the neural crest is a homogenous population of multipotent stem cells whose fates are determined post-emigration by localized environmental cues, or rather, is composed of a heterogeneous mixture of precursor cells whose individual fates are specified by intrinsic mechanisms prior to their emigration from the neural tube (reviewed in ref. With the advent of new fluorescent tracing techniques, we have reexamined the migratory behaviors and ultimate fate of ventrally migrating avian NCCs within a late wave of emigration and identified a subpopulation of lineally restricted NCCs who migrate to the contralateral dorsal root ganglia (DRG) and therein give rise to mitotically active progenitor cells that ultimately produce the majority of the nociceptive sensory neurons in the DRG. Albeit our knowledge base is rich due to a strong history of experimentation, the fact that we have yet to decipher so many key aspects of neural crest cell (NCC) behavior speaks to the challenging complexity of this transient yet vital cell population. The neural crest, the intriguing cell population that gives rise to a panoply of derivatives in the vertebrate embryo including the mesenchymal structures in the head, melanocytes and most of the peripheral nervous system still proves to be an important yet enigmatic developmental cell population to study, with applications in stem cell biology, cancer biology and clinical medicine.
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