Role of Vascular Cells in kidney pattern formation

描述(申请人提供)：过去50年围绕早期肾脏发育的诱导事件的研究主要集中在两种主要的细胞类型，间充质细胞和上皮细胞。其他器官，如肝脏和胰腺，最近的研究表明血管细胞在早期器官发育中的作用[6，7]，在这项授权中，我们展示了我们的最新结果，证明了血管细胞在早期肾脏发育中的作用。一群表达Flk-1的血管母细胞似乎对维持间充质凝集物在输尿管芽诱导间充质向上皮转化导致肾单位形成所需的能力水平上至关重要。我们利用显微注射和电穿孔胚胎肾器官培养的新系统获得的结果表明，Wt1能够诱导血管内皮生长因子(VEGF-A)的表达。因此，我们目前的模型表明，Wt1诱导血管内皮生长因子的表达来刺激血管母细胞群，而血管母细胞群又提供了一个未知的信号，作用于间充质来刺激GDNF的表达并维持分支的形态发生。这项资助的目的是为了更全面地确定血管母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.