Directing pathfinding along the dorsolateral path - the role of EDNRB2 and EphB2 in overcoming inhibition
Directing pathfinding along the dorsolateral path - the role of EDNRB2 and EphB2 in overcoming inhibition
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DOI：
10.1242/dev.023119
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发表时间：
2008-12-15
期刊：
影响因子：
4.6
通讯作者：
Erickson, Carol A.
中科院分区：
文献类型：
--
作者：
Harris, Melissa L.;Hall, Ronelle;Erickson, Carol A.
成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线沿着迁移，而大多数其他神经嵴细胞被抑制进入这个空间。这种途径的选择已被归因于独特的，细胞自主迁移的神经嵴细胞时，他们成为指定为成黑素细胞获得的属性。通过shRNA敲低和过表达实验，我们研究了三种跨膜受体在鸡躯干背外侧寻路中的作用。我们表明，内皮素受体B2（EDNRB 2）和EphB 2都是这一过程的决定因素，而与其他物种不同的是，c-KIT不是。我们证明，EDNRB 2的过表达可以维持正常的背外侧迁移的黑素细胞在EphB 2的情况下，反之亦然，表明受体表达水平的变化调节这一途径的入侵。此外，通过异位移植，我们表明，不依赖于这些受体的激活的神经嵴细胞群可以迁移背外侧只有当这条路径是免费的抑制分子。我们的结论是，EDNRB 2和EphB 2表达的黑素细胞的要求是支持他们的迁移，帮助他们克服排斥或非允许的线索在背外侧环境。
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.