Ectopic c-kit expression affects the fate of melanocyte precursors in Patch mutant embryos.
Ectopic c-kit expression affects the fate of melanocyte precursors in Patch mutant embryos.
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DOI：
10.1006/dbio.1996.0178
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发表时间：
1996-08
影响因子：
2.7
通讯作者：
Bernhard Wehrle-Haller;Kathleen Morrison-Graham;James A. Weston
中科院分区：
文献类型：
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作者：
Bernhard Wehrle-Haller;Kathleen Morrison-Graham;James A. Weston
小鼠中的 Patch (Ph) 突变是一种包含 PDGFR α 基因的缺失，是一种隐性致死突变，在杂合子中表现出显性色素表型。为了评估 Ph 突变是否对黑素细胞发育产生细胞自主或非自主作用，我们在体外检查了来自正常和突变嵴细胞的神经嵴群体的黑色素生成潜力，以及体内黑素细胞前体（MP）的分散和存活模式。我们报告说，来自纯合 Ph 胚胎的躯干神经嵴细胞响应 Steel 因子（SlF）在体外产生色素沉着的黑素细胞。在体内，纯合 Ph 胚胎含有一个嵴衍生细胞亚群，表达 MP 特有的 c-kit 和酪氨酸酶相关蛋白 2。这些细胞开始在侧嵴迁移路径上正常迁移，但随后无法分散在真皮间充质中并随后消失。尽管 Ph 纯合子中的真皮间充质受到不利影响，但当神经嵴衍生的 MP 开始在横向通路上迁移时，Ph 胚胎中皮节细胞的 SlF mRNA 表达是正常的。相比之下，SlF 受体 c-kit 的 mRNA 在携带 Ph 突变的胚胎的体节和侧间充质中异位表达。基于 Ph 突变胚胎中 c-kit 的异位表达，以及正常和突变胚胎中观察到的 SlF 蛋白分布，我们认为对位于侧神经嵴迁移途径上的有限数量的 SlF 的竞争改变了黑素细胞的分散和存活。
The Patch (Ph) mutation in the mouse, a deletion that includes the gene for PDGFR alpha, is a recessive lethal that exhibits a dominant pigment phenotype in heterozygotes. To assess whether the Ph mutation acts cell-autonomously or non-autonomously on melanocyte development, we have examined the melanogenic potential of neural crest populations from normal and mutant crest cells in vitro and the pattern of dispersal and survival of melanocyte precursors (MPs) in vivo. We report that trunk neural crest cells from homozygous Ph embryos give rise to pigmented melanocytes in vitro in response to Steel factor (SlF). In vivo, homozygous Ph embryos contain a subpopulation of crest-derived cells that express c-kit and tyrosinase-related protein-2 characteristic of MPs. These cells begin to migrate normally on the lateral crest migration pathway, but then fail to disperse in the dermal mesenchyme and subsequently disappear. Although dermal mesenchyme is adversely affected in Ph homozygotes, SlF mRNA expression by the cells of the dermatome is normal in Ph embryos when neural crest-derived MPs start to migrate on the lateral pathway. In contrast, mRNA for the SlF receptor, c-kit, was observed to be ectopically expressed in somites and lateral mesenchyme in embryos carrying the Ph mutation. Based on this ectopic expression of c-kit in Ph mutant embryos, and the observed distribution of SlF protein in normal and mutant embryos, we suggest that competition for limited amounts of SlF localized on the lateral neural crest migration pathway alters melanocyte dispersal and survival.