Regulators of migration in Xenopus cranial neural crest cells

颅神经嵴细胞（CNC）塑造脊椎动物的面部。它们具有两个特殊的特性：多能性和运动性。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向迁移时逐步分化。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、趋化因子和粘附因子为迁移的CNC构建了特定的微环境。虽然CNC的诱导和迁移是一个很有特征的过程，但人们对分子知之甚少，分子引导CNC沿着特定的路线到达最终目的地。此外，这些导航器是否同时调节CNC的终端分化也是一个尚未解决的问题。本研究旨在通过对twist依赖性调节因子进行基因表达筛选和对假定的候选基因进行功能分析，确定控制CNC迁移的因素。此外，还研究了原钙粘蛋白PCNS在Wnt-5a/Ror2信号传导中的作用。这些研究从临床角度来看很重要，因为一些CNC特异性基因如snail和cadherin-11在转移性肿瘤中表达上调，而Twist和kit等其他基因的突变会导致严重的先天性疾病。

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.