Role of Vascular Cells in kidney pattern formation

过去50年来，围绕早期肾脏发育的诱导事件的研究已经 重点研究了两种主要的细胞类型，间充质细胞和上皮细胞。最近在其他机构的工作，如 与肝脏和胰腺一样，已经表明血管细胞在早期器官发育中的作用[6，7] 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。一个 表达Flk-1的血管母细胞群在维持间充质凝集物方面似乎是至关重要的 在输尿管芽诱导间充质转化为上皮所需的能力水平上 导致肾素形成的转换。我们目前的结果，是使用一种新的系统获得的 显微注射和电穿孔胚胎肾器官培养，证明Wt1能够诱导 血管内皮生长因子-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以刺激血管母细胞群，这反过来又提供了 作用于间充质以刺激GDNF表达和维持分支的不明信号 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，以及它如何参与刺激分枝和胚胎肾脏的图案化。

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.