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

神经嵴迁移：通过非经典 Wnt 通路 Syndecan-4 和趋化因子之间的相互作用进行控制

• 批准号: BB/D017521/1
• 负责人: Roberto Mayor
• 金额: $ 38.77万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD017521%2F1
• 关键词: Neural; crest; migration; control; interactions

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.

神经嵴是在所有脊椎动物胚胎中发现的迁移细胞群，产生几种不同的细胞类型。在头部，这些细胞形成面部的特定组成部分，在身体中，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，其中一些基因的突变是人类某些疾病的原因，如Hirschprungs和Saethre-Chotzen疾病和Waardenburg-Shah综合征。神经嵴细胞在神经板的边缘形成，嵴细胞从这里迁移到胚胎的不同部位，在那里它们分化成各种细胞类型。由于它们非凡的迁移能力，神经嵴细胞被称为“胚胎的探索者”。控制神经嵴迁移的分子机制似乎与触发癌细胞转移的事件相似。然而，我们仍然对迁移的嵴细胞如何找到正确的目的地几乎一无所知。在这个项目中，我们将分析3个不同的，显然没有相关的，在神经嵴迁移分子的作用。一种可能性是细胞被其靶位点产生的特定分子吸引（趋化性）。其中一种分子可能是一种名为SDF-1的蛋白质。这是触发白色血细胞趋化性的因素，我们将在这里测试在神经嵴迁移过程中是否发生类似的事情。此外，SDF-1及其受体（CXCR 4）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将是在神经嵴迁移过程中研究的第二种分子。我们的初步数据还表明，Syndecan-4与另一种称为非经典Wnt信号传导的信号传导途径相互作用。我们的实验室是第一个表明非经典Wnt信号传导是神经嵴迁移所必需的。总的来说，似乎所有这三种分子都参与了神经嵴迁移，并且它们彼此相互作用。总之，我们将测试SDF-1/CXCR 4，Syndecan-4和非经典途径控制神经嵴迁移以及它们在此事件中相互作用的想法。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一般。这项工作所揭示的原理也将与理解癌细胞迁移入侵其他组织有关。此外，我们将了解Wnt信号控制细胞迁移的机制。

项目成果

In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity.

• DOI: 10.1083/jcb.201402093
• 发表时间: 2014-07-07
• 期刊: The Journal of cell biology
• 作者: Kuriyama S;Theveneau E;Benedetto A;Parsons M;Tanaka M;Charras G;Kabla A;Mayor R
• 通讯作者: Mayor R