Molecular function of Tbx18 in ureter development

Tbx18在输尿管发育中的分子功能

• 批准号: 84948123
• 负责人: Professor Dr. Andreas Kispert
• 金额: --
• 依托单位: Institut für Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/84948123?language=en
• 关键词: Molecular; function; Tbx18; ureter; development

Formation of the ureter relies on a multi-step developmental program that is characterized by the in-teraction of different mesenchymal and epithelial cell lineages of the early metanephric field. Recent findings have revealed the importance of the ureteric mesenchyme and the T-box transcription factor Tbx18 therein for this process. In Tbx18-/- mice, the ureteric mesenchyme disperses and remains undifferentiated leading to hydroureter formation by functional obstruction. Here, we want to define the molecular pathways that confer the spatial restriction of Tbx18 expression in the early metanephric field and characterize by genetic loss- and gain-of-function approaches the genetic circuits that act downstream of Tbx18 to mediate its function in the ureteric mesenchyme. The functional significance of ephrin-signaling and Sox9 transcriptional activity in compartmentalization and aggregation of urete-ric mesenchyme shall be studied. Micro-array analysis of Tbx18-/- ureters shall identify additional mediators of Tbx18 function but also of Bmp- and Shh-signaling in this tissue. We expect from these experiments new insight into the genetic control of early ureter development and into the etiology of congenital malformation of the urinary tract.

输尿管的形成依赖于一个多步骤的发育程序，其特征是不同的后肾区间充质和上皮细胞谱系的相互作用。最近的发现揭示了输尿管间充质和其中的T-box转录因子TBX18在这一过程中的重要性。在TBX18-/-小鼠中，输尿管间充质弥散并保持未分化状态，导致功能性梗阻形成输尿管积水。在这里，我们想要定义的分子途径，赋予空间限制的TBX18表达在早期的后肾区，并以遗传功能丧失和功能获得的途径为特征的遗传回路的下游作用，以调节其在输尿管间充质中的功能。本研究拟探讨EPhin信号和Sox9转录活性在尿素间充质区域化和聚集过程中的功能意义。对TBX18-/-输尿管的微阵列分析应确定该组织中的TBX18功能以及BMP和Shh信号的其他介体。我们期待从这些实验中对输尿管早期发育的基因控制和先天性尿路畸形的病因学有新的见解。