Henion P D, Weston J A
Institute of Neuroscience, University of Oregon, Eugene 97403, USA.
Development. 1997 Nov;124(21):4351-9. doi: 10.1242/dev.124.21.4351.
The trunk neural crest of vertebrate embryos is a transient collection of precursor cells present along the dorsal aspect of the neural tube. These cells migrate on two distinct pathways and give rise to specific derivatives in precise embryonic locations. One group of crest cells migrates early on a ventral pathway and generates neurons and glial cells. A later-dispersing group migrates laterally and gives rise to melanocytes in the skin. These observations raise the possibility that the appearance of distinct derivatives in different embryonic locations is a consequence of lineage restrictions specified before or soon after the onset of neural crest cell migration. To test this notion, we have assessed when and in what order distinct cell fates are specified during neural crest development. We determined the proportions of different types of precursor cells in cultured neural crest populations immediately after emergence from the neural tube and at intervals as development proceeds. We found that the initial neural crest population was a heterogeneous mixture of precursors almost half of which generated single-phenotype clones. Distinct neurogenic and melanogenic sublineages were also present in the outgrowth population almost immediately, but melanogenic precursors dispersed from the neural tube only after many neurogenic precursors had already done so. A discrete fate-restricted neuronal precursor population was distinguished before entirely separate fate-restricted melanocyte and glial precursor populations were present, and well before initial neuronal differentiation. Taken together, our results demonstrate that lineage-restricted subpopulations constitute a major portion of the initial neural crest population and that neural crest diversification occurs well before overt differentiation by the asynchronous restriction of distinct cell fates. Thus, the different morphogenetic and differentiative behavior of neural crest subsets in vivo may result from earlier cell fate-specification events that generate developmentally distinct subpopulations that respond differentially to environmental cues.
脊椎动物胚胎的躯干神经嵴是沿神经管背侧分布的一群短暂存在的前体细胞。这些细胞沿两条不同的路径迁移，并在精确的胚胎位置产生特定的衍生物。一组嵴细胞早期沿腹侧路径迁移，产生神经元和神经胶质细胞。另一组较晚分散的细胞则向侧面迁移，在皮肤中产生黑素细胞。这些观察结果提示，在不同胚胎位置出现不同的衍生物可能是神经嵴细胞迁移开始之前或之后不久所确定的谱系限制的结果。为了验证这一观点，我们评估了在神经嵴发育过程中不同细胞命运是何时以及以何种顺序确定的。我们测定了从神经管刚分离出来时以及随着发育进行每隔一段时间培养的神经嵴群体中不同类型前体细胞的比例。我们发现，最初的神经嵴群体是前体细胞的异质混合物，其中近一半产生单表型克隆。在神经嵴细胞向外生长的群体中几乎立即也存在不同的神经源性和黑素源性亚谱系，但黑素源性前体细胞在许多神经源性前体细胞已经从神经管分散之后才开始分散。在完全分离的命运受限的黑素细胞和神经胶质前体细胞群体出现之前，以及在最初的神经元分化之前很久，就已经区分出了一个离散的命运受限的神经元前体细胞群体。综合来看，我们的结果表明，谱系受限的亚群体构成了最初神经嵴群体的主要部分，并且神经嵴的多样化在明显分化之前就通过不同细胞命运的异步限制而发生。因此，神经嵴亚群在体内不同的形态发生和分化行为可能是由早期的细胞命运指定事件导致的，这些事件产生了发育上不同的亚群体，它们对环境线索有不同的反应。
