Role of Vascular Cells in kidney pattern formation

描述（由申请人提供）：过去50年对围绕早期肾脏发育的诱导事件的研究集中在两种主要细胞类型，间充质和上皮。最近在其他器官（如肝脏和胰腺）中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，我们提出了我们最近的研究结果，证明了血管细胞在早期肾脏发育中的作用。Flk-1表达的成血管细胞的人口似乎是至关重要的，在维持间充质冷凝物的能力水平，这是所需的输尿管芽诱导间充质上皮转化，导致肾单位的形成。我们目前的研究结果，使用一种新的系统，显微注射和电穿孔胚胎肾器官培养，表明Wt 1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，Wt 1诱导VEGF的表达，以刺激成血管细胞的人口，这反过来又提供了一个尚未确定的信号，作用于间充质，刺激GDNF的表达和维持分支形态发生。这项资助的目的是更全面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形成。

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.