Neural crest migration: control by interactions between the non-canonical Wnt pathway Syndecan-4 and chemokines

神经嵴是在所有脊椎动物胚胎中发现的一种迁移细胞群，它产生几种不同的细胞类型。在头部，这些细胞形成脸部的特定成分，在体内，它们产生周围神经系统，皮肤色素等。神经嵴细胞的发育需要几个基因，其中一些基因在人类中的突变会导致某些疾病，如Hirschprungs和saethree - chotzen病和Waardenburg-Shah综合征。神经嵴细胞在神经板的边缘形成，正是从这里，嵴细胞迁移到胚胎的不同部位，在那里它们分化成各种各样的细胞类型。由于神经嵴细胞具有非凡的迁移能力，因此被称为“胚胎探险家”。控制神经嵴迁移的分子机制似乎与引发癌细胞转移的事件相似。然而，对于迁移的嵴细胞如何找到正确的目的地，我们几乎一无所知。在这个项目中，我们将分析三种不同的，显然不相关的分子在神经嵴迁移中的作用。一种可能是细胞被目标部位产生的特定分子所吸引（趋化性）。其中一个分子可能是一种叫做SDF-1的蛋白质。这是触发白细胞趋化的因素，我们将在这里测试在神经嵴迁移过程中是否发生了类似的事情。此外，SDF-1及其受体（CXCR4）与另一种称为Syndecan-4的分子相互作用。我们实验室的初步证据表明Syndecan-4也是NC迁移所必需的；因此，Syndecan-4将是神经嵴迁移过程中第二个需要研究的分子。我们的初步数据还表明Syndecan-4与另一种称为非规范Wnt信号通路相互作用。我们的实验室是第一个证明非规范Wnt信号是神经嵴迁移所必需的。综上所述，这三种分子似乎都与神经嵴迁移有关，而且它们之间相互作用。总之，我们将验证SDF-1/CXCR4、Syndecan-4和非规范通路控制神经嵴迁移，并在此过程中相互作用的观点。这项研究将教会我们很多关于神经嵴迁移的分子机制，特别是关于细胞迁移的分子机制。这项工作揭示的原理也将与理解癌细胞迁移侵入其他组织的迁移有关。此外，我们将了解Wnt信号控制细胞迁移的机制。

The neural crest is a migratory cell population found in all vertebrate embryos, that generates several different cell types. In the head, these cells form specific components of the face, and in the body they generate the peripheral nervous system, skin pigment, etc. Several genes are required for the development of neural crest cells, and mutations of some of these genes in humans are responsible for certain diseases, such as Hirschprungs and Saethre-Chotzen diseases and Waardenburg-Shah syndrome. The neural crest cell forms at the border of the neural plate, and it is from here that the crest cells migrate to different parts of the embryo where they differentiate into a wide range of cell types. Because of their extraordinary ability to migrate, the neural crest cells have been called the 'explorer of the embryo'. The molecular mechanisms that control neural crest migration seem to be similar to the events that trigger metastasis in cancer cells. However, we still know almost nothing about how the migrating crest cells can find their correct destinations. In this project we will analyze the role of 3 different, apparently no related, molecules during neural crest migration. One possibility is that cells are attracted by specific molecules produced by their target sites (chemotaxis). One of the molecules may be a protein called SDF-1. This is the factor that triggers chemotaxis in white blood cells and we will test here if something similar occurs during neural crest migration. Furthermore, SDF-1 and its receptor (CXCR4) interact with another molecule called Syndecan-4. Preliminary evidence in our laboratory indicates that Syndecan-4 is also required for NC migration; thus, Syndecan-4 will be a second molecule to study during neural crest migration. Our preliminary data also indicate that Syndecan-4 interacts with another signalling pathway called non-canonical Wnt signalling. Our laboratory was the first to show that non-canonical Wnt signalling is required for neural crest migration. Taken together, it seems that all three of these molecules are involved in neural crest migration and that they interact with each other. In conclusion, we will test the idea that SDF-1/CXCR4, Syndecan-4 and the non-canonical pathway control neural crest migration and that they interact during this event. This research will teach us a lot about the molecular mechanism of neural crest migration in particular, and about cell migration in general. The principles uncovered by this work will also be relevant to understanding the migration of cancer cells which migrate to invade other tissues. In addition we will learn about the mechanism by which Wnt signalling controls cell migration.