Directional cell migration in vivo Wnt at the crest
Directional cell migration in vivo Wnt at the crest
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DOI：
10.4161/cam.2.4.6747
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发表时间：
2008-10-01
影响因子：
3.2
通讯作者：
Mayor, Roberto
中科院分区：
文献类型：
--
作者：
Carmona-Fontaine, Carlos;Matthews, Helen;Mayor, Roberto
定向细胞迁移对于几乎所有生物体在胚胎发育期间、在成年生活中是必不可少的，并且有助于病理条件。这在胚胎发生过程中尤其重要，在胚胎发生过程中，细胞必须在正确、精确的位置结束，以建立正常的胚胎。许多细胞已经通过遵循通常由其靶组织分泌的化学引诱物的梯度来解决这个问题。我们最近的研究发现了一种替代的、互补的机制，在这种机制中，细胞内信号能够在没有任何外部趋化剂的情况下产生细胞极性和定向迁移。我们使用神经嵴细胞研究细胞迁移在体内，通过执行胚胎发育过程中迁移的神经嵴细胞的现场成像。我们发现，平面细胞极性（PCP）或非经典Wnt信号通路与蛋白聚糖syndecan-4相互作用，以控制细胞突起产生的方向，从而控制迁移的方向。通过使用体内FRET成像分析小GTP酶的活性，我们表明PCP信号传导激活RhoA，而多配体蛋白聚糖-4抑制Rac，两者都在神经嵴细胞的后部。在这里，我们讨论了一个模型，这些信号被整合在体内产生定向迁移。
Directional cell migration is essential for almost all organisms during embryonic development, in adult life and contributes to pathological conditions. This is particularly critical during embryogenesis where it is essential that cells end up in their correct, precise locations in order to build a normal embryo. Many cells have solved this problem by following a gradient of a chemoattractant usually secreted by their target tissues. Our recent research has found an alternative, complimentary, mechanism where intracellular signals are able to generate cell polarity and directional migration in absence of any external chemoattactant. We used neural crest cells to study cell migration in vivo, by performing live imagining of the neural crest cell migrating during embryo development. We show that the Planar Cell Polarity (PCP) or non-canonical Wnt signaling pathway interacts with the proteoglycan syndecan-4 to control the direction in which cell protrusions are generated, and in consequence, the direction of migration. By analyzing the activity of the small GTPases using in vivo FRET imaging we showed that PCP signaling activates RhoA, while syndecan-4 inhibits Rac, both at the back of the neural crest cell. Here we discuss a model where these signals are integrated to generate directional migration in vivo.