Role of Vascular Cells in kidney pattern formation

描述（由申请人提供）：过去50年关于早期肾脏发育的诱导事件的研究主要集中在两种主要细胞类型，间质和上皮细胞。最近在其他器官（如肝脏和胰腺）的研究表明，血管细胞在早期器官发育中的作用[6,7]。在本研究中，我们展示了血管细胞在早期肾脏发育中的作用。表达flk -1的成血管细胞群似乎在维持输尿管芽诱导间质向上皮转化从而形成肾单位所需的间质凝聚物的能力水平方面起着至关重要的作用。我们目前的研究结果表明，Wt1能够诱导血管内皮生长因子（VEGF-A）的表达，该结果是通过微注射和电穿孔胚胎肾器官培养的新系统获得的。因此，我们目前的模型表明，Wt1诱导VEGF表达以刺激成血管细胞群体，这反过来又提供了一种尚未确定的信号，该信号作用于间质以刺激GDNF表达并维持分支形态发生。这项资助的目的是为了更充分地确定成血管细胞信号的分子性质，以及它如何参与刺激分支和胚胎肾脏的模式。

DESCRIPTION (provided by applicant): The previous fifty years of study on the inductive events that surround early kidney development have focused on the two major cell types, the mesenchyme and epithelium. Recent work in other organs, such as liver and pancreas, have indicated a role for vascular cells in early organ development [6, 7], In this grant we present our recent results demonstrating a role for vascular cells in early kidney development. A population of Flk-1-expressing angioblasts appears to be crucial in maintaining mesenchymal condensates at a level of competence that is required for the ureteric bud to induce the mesenchymal to epithelial conversion that results in the formation of nephrons. Our present results, obtained using a novel system for microinjecting and electroporating embryonic kidney organ cultures, demonstrates that Wt1 is able to induce expression of vascular endothelial growth factor (VEGF-A). Thus, our current model suggests that Wt1 induces expression of VEGF to stimulate the angioblast population, which in turn provides an as yet unidentified signal that acts on the mesenchyme to stimulate expression of GDNF and maintain branching morphogenesis. The aims of this grant are designed to more fully determine the molecular nature of the angioblast signal, and how it may be involved in stimulating branching, and patterning the embryonic kidney.