THE ROLE OF WNT SIGNALING IN DEVELOPMENT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项试点提案，要求资金支持三位RCMI研究人员之间的合作研究。该提案的中心主题是利用小鼠基因敲除研究来深入了解重要信号通路在发育过程中的作用。基因破坏为理解复杂的生物过程提供了有力的工具。将使用一种新的高效的“靶向基因捕获”技术产生携带感兴趣基因单一突变的转基因小鼠系。这些基因敲除系将由三位研究者各自使用。目前研究计划的重点将是研究Wnt信号通路在发育过程中的作用。clemen1是一种编码Wnt信号通路抑制受体的基因，已经建立了小鼠敲除系，初步研究将集中在这些突变系的表型分析上。利用这些krm1突变体，三位研究人员将验证krm1功能丧失导致Wnt信号增加导致以下异常途径的基本假设：1)视网膜血管发育，2)T细胞发育和3)B细胞发育。由于产生小鼠敲除的费用，这是一种非常有效和经济的方法，可以共享资源，促进RCMI研究人员之间的合作。预计试点项目的结果将成为新的研究补助金的基础，并对RCMI的总体目标作出重大贡献。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot proposal requesting funds to support collaborative research between three RCMI investigators with shared research interests. A central theme of the proposal is the use of mouse gene knockout studies to gain insights into the role of important signaling pathways during development. Gene disruption provides a powerful tool towards understanding complex biological processes. Transgenic mouse lines carrying single mutations in genes of interest will be generated using a new highly efficient ¿Targeted gene trapping¿ technique. These knockout lines will be used by each of the three investigators. The focus of the current research proposal will be to examine the role of Wnt signaling pathway during development. A mouse knockout line for the Kremen1, a gene which encodes an inhibitory receptor for the Wnt signaling pathway, has already been established and the initial studies will focus on phenotypic analyses of these mutant lines. Utilizing these krm1 mutants, the three investigators will test the basic hypothesis that loss of Krm1 function results in increased Wnt signaling leading to the following aberrant pathways: 1) retinal vascular development, 2) T cell development and 3) B cell development. Because of the expense of generating mouse knockouts, this is a very efficient and economical approach of sharing resources and promoting collaboration among RCMI investigators. It is expected that the results from the pilot project will be the basis of new research grants and contribute significantly towards the overall goals of the RCMI.