Harris Melissa L, Hall Ronelle, Erickson Carol A
University of California, Davis, Department of Molecular and Cellular Biology, One Shields Avenue, Davis, CA 95616, USA.
Development. 2008 Dec;135(24):4113-22. doi: 10.1242/dev.023119. Epub 2008 Nov 12.
Neural crest cells that become pigment cells migrate along a dorsolateral route between the ectoderm and the somite, whereas most other neural crest cells are inhibited from entering this space. This pathway choice has been attributed to unique, cell-autonomous migratory properties acquired by neural crest cells when they become specified as melanoblasts. By shRNA knockdown and overexpression experiments, we investigated the roles of three transmembrane receptors in regulating dorsolateral pathfinding in the chick trunk. We show that Endothelin receptor B2 (EDNRB2) and EphB2 are both determinants in this process, and that, unlike in other species, c-KIT is not. We demonstrate that the overexpression of EDNRB2 can maintain normal dorsolateral migration of melanoblasts in the absence of EphB2, and vice versa, suggesting that changes in receptor expression levels regulate the invasion of this pathway. Furthermore, by heterotopic grafting, we show that neural crest cell populations that do not rely on the activation of these receptors can migrate dorsolaterally only if this path is free of inhibitory molecules. We conclude that the requirement for EDNRB2 and EphB2 expression by melanoblasts is to support their migration by helping them to overcome repulsive or non-permissive cues in the dorsolateral environment.
分化为色素细胞的神经嵴细胞沿着外胚层和体节之间的背外侧路径迁移，而大多数其他神经嵴细胞则被阻止进入这个空间。这种路径选择归因于神经嵴细胞在分化为成黑素细胞时获得的独特的细胞自主迁移特性。通过短发夹RNA敲低和过表达实验，我们研究了三种跨膜受体在调节鸡胚躯干背外侧路径寻找中的作用。我们发现内皮素受体B2（EDNRB2）和EphB2都是这一过程的决定因素，并且与其他物种不同的是，c-KIT不是。我们证明，在没有EphB2的情况下，EDNRB2的过表达可以维持成黑素细胞正常的背外侧迁移，反之亦然，这表明受体表达水平的变化调节了这条路径的侵入。此外，通过异位移植，我们发现不依赖于这些受体激活的神经嵴细胞群体只有在这条路径没有抑制分子时才能背外侧迁移。我们得出结论，成黑素细胞对EDNRB2和EphB2表达的需求是通过帮助它们克服背外侧环境中的排斥或不允许信号来支持其迁移。
