Carmona-Fontaine Carlos, Matthews Helen, Mayor Roberto
Department of Cell and Developmental Biology, University College London, London, UK.
Cell Adh Migr. 2008 Oct-Dec;2(4):240-2. doi: 10.4161/cam.2.4.6747. Epub 2008 Oct 5.
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.
定向细胞迁移在胚胎发育、成年期的几乎所有生物体中都至关重要，并与病理状况相关。这在胚胎发生过程中尤为关键，因为细胞必须最终处于其正确、精确的位置才能构建正常胚胎。许多细胞通过遵循通常由其靶组织分泌的趋化因子梯度来解决这个问题。我们最近的研究发现了另一种互补机制，即细胞内信号能够在没有任何外部趋化因子的情况下产生细胞极性和定向迁移。我们利用神经嵴细胞通过对胚胎发育过程中迁移的神经嵴细胞进行实时成像来研究体内细胞迁移。我们表明，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，进而控制迁移方向。通过使用体内FRET成像分析小GTP酶的活性，我们发现PCP信号在神经嵴细胞的后部激活RhoA，而syndecan-4抑制Rac。在此我们讨论一个模型——这些信号在该模型中整合以在体内产生定向迁移。
