Luo Rushu, Gao Juan, Wehrle-Haller Bernhard, Henion Paul D
Neurobiotechnology Center and Department of Neuroscience, Ohio State University, 105 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA.
Development. 2003 Jan;130(2):321-30. doi: 10.1242/dev.00213.
Clonal and lineage analyses have demonstrated that although some neural crest cells have the ability to generate multiple cell types and display self-renewal ability, other crest cells generate a single or limited repertoire of cell types. However, it is not yet clear when, and in what order, crest cells become specified to adopt a particular fate. We report that the receptor tyrosine kinases TrkC and C-Kit are expressed by distinct neural crest subpopulations in vitro. We then analyzed the lineages of individual receptor-expressing crest cells and found that TrkC-expressing cells that have just emerged from the neural tube give rise to clones containing neurons or glial cells, or both, but never produce melanocytes. A short time later, TrkC-expressing cells only generate pure neuronal clones. By contrast, from their earliest appearance in neural tube outgrowths, C-Kit-expressing cells invariably give rise to clones containing only melanocytes. Our results directly demonstrate that distinct neurogenic and melanogenic sublineages diverge before or soon after crest cells emerge from the neural tube, that fate-restricted precursors are present in nascent neural crest populations and that these sublineages can be distinguished by their cell type-specific expression of receptor tyrosine kinases.
克隆分析和谱系分析表明，尽管一些神经嵴细胞有能力生成多种细胞类型并表现出自我更新能力，但其他嵴细胞只能生成单一或有限种类的细胞类型。然而，目前尚不清楚嵴细胞何时以及按照何种顺序被指定采用特定的命运。我们报告称，受体酪氨酸激酶TrkC和C-Kit在体外由不同的神经嵴亚群表达。然后我们分析了单个表达受体的嵴细胞的谱系，发现刚从神经管中出现的表达TrkC的细胞会产生包含神经元或神经胶质细胞，或两者都有的克隆，但从不产生黑素细胞。短时间后，表达TrkC的细胞只产生纯神经元克隆。相比之下，从它们最早出现在神经管生长物中开始，表达C-Kit的细胞总是产生仅包含黑素细胞的克隆。我们的结果直接表明，不同的神经源性和黑素源性亚谱系在嵴细胞从神经管中出现之前或之后不久就开始分化，命运受限的前体细胞存在于新生的神经嵴群体中，并且这些亚谱系可以通过它们对受体酪氨酸激酶的细胞类型特异性表达来区分。
