Role of Vascular Cells in kidney pattern formation

血管细胞在肾脏模式形成中的作用

• 批准号: 7991420
• 负责人: Jordan A Kreidberg
• 金额: $ 8.45万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-15 至 2010-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991420
• 关键词: Angioblast; Blood Vessels; Cells; Competence; Development; Elements; Embryo; Epithelial; Epithelium; Event; Fibrinogen; GDNF gene; Genes; Grant; Histologic; Human; Invaded; Kidney; Liver; Lung; Mesenchymal; Mesenchyme; Metanephric Diverticulum; Modeling; Molecular; Morphogenesis; Mutation; Nature; Nephrons; Organ; Organ Culture Techniques; Pancreas; Pattern; Pattern Formation; Physical condensation; Population; Process; Role; Signal Transduction; Staging; Structure of mesonephric duct; System; Transcription Coactivator; Tubular formation; Urogenital ridge structure; VEGFA gene; Vascular Endothelial Growth Factors; WT1 gene; Work; cell type; design; nephrogenesis; novel; transcription factor

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.

过去50年对早期肾脏发育诱导事件的研究， 集中在两种主要的细胞类型，间充质和上皮。其他机构最近的工作，例如 如肝脏和胰腺，已经表明血管细胞在早期器官发育中的作用[6，7]，在这方面， 格兰特，我们提出了我们最近的结果，证明了血管细胞在早期肾脏发育中的作用。一 表达Flk-1的成血管细胞群体似乎在维持间充质凝聚物中至关重要 在输尿管芽诱导间充质细胞向上皮细胞分化所需的能力水平上， 导致肾单位形成的转化过程。我们目前的结果，获得了使用一种新的系统， 显微注射和电穿孔胚胎肾器官培养，证明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群，这反过来又提供了迄今为止的 作用于间充质以刺激GDNF表达并维持分支的未鉴定信号 形态发生这项资助的目的是为了更全面地确定 成血管细胞信号，以及它如何参与刺激分支和胚胎肾的形成。