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Regulators of migration in Xenopus cranial neural crest cells

非洲爪蟾颅神经嵴细胞迁移的调节因子

基本信息

批准号：
175379949
负责人：
Professorin Dr. Doris Wedlich
金额：
--
依托单位：
Abteilung für Zell- und Entwicklungsbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/175379949?language=en
关键词：
Regulators migration Xenopus cranial neural

项目摘要

The cranial neural crest cells (CNC) shape the face of vertebrates. They possess two exceptional properties: pluripotency and motility. These pluripotent cells differentiate to melanocytes, nerves and ganglia, cartilage and bones. They differentiate stepwise while migrating dorsolaterally on defined routes. During this process the microenvironment of the migration route decides about the cell fate. Growth factors, chemokines and adhesion factors build up the specific microenvironment for the migrating CNC. While induction and emigration of CNC are well characterized processes little is known about molecules, which navigate CNC on specific routes to their final destination. Furthermore, it is a still unsolved question whether these navigators simultaneously regulate the terminal differentiation of CNC. This study aims to identify factors that control migration of CNC by performing a gene expression screen of Twist-dependent regulators and by functional analyses of putative candidate genes. In addition, the role of protocadherin PCNS in relation to Wnt-5a/Ror2 signalling is investigated. These studies are important from clinical views because some of the CNC specific genes like snail and cadherin-11 are upregulated in metastatic tumors and mutations of others like Twist and kit lead to serious congenital disorders.

脑神经脊细胞(Cnc)塑造脊椎动物的面部。它们具有两个特殊的性质：多能性和能动性。这些多能细胞分化为黑素细胞、神经和神经节、软骨和骨骼。它们在确定的路线上背侧迁徙时，会逐步分化。在这个过程中，迁移路径的微环境决定了细胞的命运。生长因子、趋化因子和黏附因子为迁移的数控系统构建了特定的微环境。虽然数控系统的诱导和迁出过程是很好的特征，但人们对分子知之甚少，这些分子在特定的路线上导航数控系统到达最终目的地。此外，这些导航器是否同时调节数控系统的终端分化仍是一个悬而未决的问题。本研究旨在通过对Twist依赖的调控因子进行基因表达筛选和对可能的候选基因进行功能分析来确定控制CNC迁移的因素。此外，还研究了Protocadherin PCNS在Wnt-5a/Ror2信号转导中的作用。从临床角度来看，这些研究很重要，因为一些cnc特有的基因，如蜗牛和钙粘蛋白-11，在转移性肿瘤中上调，而其他基因的突变，如Twist和Kit，会导致严重的先天性疾病。