Mechanisms of Wnt signaling in cell polarity and cell migration

细胞迁移的适当控制是后生动物发育的关键。定向迁移需要保密 细胞外信号通过细胞表面受体起作用，以引导这些细胞的迁移。分泌的Wnt 蛋白质是一类主要的细胞外信号的成员，其定向细胞和组织极性，指定细胞 命运和许多细胞类型的直接细胞迁移。Wnt信号级联基因的突变是 与人类癌症的发展有关;因此，了解Wnt蛋白如何发挥作用具有重要意义。 生物医学的重要性。C.线虫的神经细胞迁移是一个很好的模型， 由于这种生物体的基因操纵，信号通路调节细胞极性和迁移 以及直接观察迁移细胞的能力。我们之前发现了CAM-1基因的突变， 其编码Ror型受体酪氨酸激酶（RTK），所述RTK是引导迁移细胞向其适当位置迁移所必需的。 目的地我们发现，CAM-1的行为，显然是作为一个传统的RTK，定向神经元极性。我们 提出实验来解释其在定向神经元极性中的作用机制。另外我们有 发现了41个影响细胞迁移的新突变，包括cfz-2中的第一个突变，一个C.卷叶秀丽线虫 受体，其参与Wnt信号传导。我们建议使用大规模的DNA测序技术， 至少有三个新的迁移基因识别和机械理解 这些新基因的作用将为控制细胞迁移的过程提供新的见解。

The proper control of cell migration is critical for metazoan development. Directed migration requires secreted extracellular signals that act through cell surface receptors to guide the migrations of those cells. Secreted Wnt proteins are members of a major class of extracellular signals that orient cell and tissue polarity, specify cell fates, and direct cell migrations of numerous cell types. Mutation of Wnt signaling cascade genes are associated with the development of human cancers; thus understanding how Wnt proteins act is of significant biomedical importance. C. elegans neuronal cell migration serves as an excellent model for understanding how signaling pathways modulate cell polarity and migration due to the fascile genetic manipulation of this organism and the ability to visualize directly the migrating cells. We previously identified mutations in the CAM-1 gene, which encodes a Ror type receptor tyrosine kinase (RTK) required for directing migrating cells to their proper destination. We found that CAM-1 acts, apparently as a traditional RTK, to orient neuronal polarity. We propose experiments to decipher its mechanism of action in orienting neuronal polarity. In addition, we have identified 41 new mutations that affect cell migration, including the first mutation in cfz-2, a C. elegans Frizzled receptor, which is involved in Wnt signaling. We propose to use large-scale DNA sequencing to rapidly clone at least three of our new migration genes from this screen. The identification and mechanistic understanding of the roles of these new genes will provide new insight into the processes that control cell migration.