WNT GENES AND SIGNALING IN XENOPUS

Wnt是一种分泌型配体，可激活受体介导的信号通路。脊椎动物Wnt及其信号传导通路在轴的特化、中胚层和神经系统的模式化、肢体的极性和器官发生中起着关键作用。当不适当地激活时，Wnt途径的组分可能与各种人类癌症，特别是结肠直肠癌和黑色素瘤有关。目前的提案代表了一个竞争性的继续申请，以维持我们在非洲爪蟾中Wnt基因及其信号通路的工作的资金。由于先前的具体目标在很大程度上已经得到答复，我们目前的建议提出了新的具体目标，以解决最近因先前的支持而产生的问题。虽然许多以前的具体目标问胚胎学问题，目前的重点是Wnt信号转导。目的1使用酵母双杂交筛选和质谱分析来鉴定Wnt-1/Frizzled-1途径的新组分。目的2研究我们在前两个项目期间发现的独特的Wnt-5a/Frizzled-2途径的生物化学。目的3研究Wnt信号转导的靶基因及其在发育中的作用。鉴于Wnt-1信号通路在进化中的高度保守性，在非洲爪蟾中的这项工作的结果可能会继续直接应用于其他脊椎动物中的Wnt信号。

Wnts are secreted ligands which activate receptor-mediated signaling pathways. Vertebrate Wnts and their signaling pathways have been implicated in playing key roles in axis specification, in patterning mesoderm and the nervous system, in providing polarity to limbs, and in organogenesis. When inappropriately activated, components of the Wnt pathways may be linked to various human cancers notably colorectal cancer and melanoma. The current proposal represents a competing continuation application, to maintain funding for our work on Wnt genes and their signaling pathways in Xenopus. As the previous specific aims have largely been answered, our present proposal introduces new specific aims to address recent questions arising from this prior support. Whereas many of the previous specific aims asked embryological questions, the current focus is on Wnt signal transduction. Aim 1 uses yeast-two hybrid screens, and mass spectroscopy analysis, to identify new components of the Wnt-1/Frizzled-1 pathway. Aim 2 investigates the biochemistry of the distinct Wnt-5a/Frizzled-2 pathway which we discovered in the prior two project periods. Aim 3 investigates the target genes of Wnt signaling and their functions in development. Given the high degree of conservation of the Wnt-1 signaling pathway in evolution, it is likely the results of this work in Xenopus will continue to directly apply to Wnt signaling in other vertebrates.