Molecular function of Tbx18 in ureter development

输尿管的形成依赖于一个多步骤的发育程序，其特征在于早期后肾区不同间充质和上皮细胞谱系的相互作用。最近的研究结果揭示了输尿管间充质和T-box转录因子Tbx18在这一过程中的重要性。在Tbx18-/-小鼠中，输尿管间充质分散并保持未分化，导致功能性梗阻导致输尿管积水形成。在这里，我们要定义的分子途径，赋予Tbx18的表达在早期后肾领域的空间限制和特征的遗传损失和获得的功能的方法的遗传电路的作用Tbx18的下游介导其在输尿管间充质的功能。肝配蛋白信号传导和Sox 9转录活性在输尿管间质区室化和聚集中的功能意义有待研究。Tbx18-/-输尿管的微阵列分析应识别Tbx18功能的其他介质，以及该组织中BMP和Shh信号传导的介质。我们期望从这些实验中对早期输尿管发育的遗传控制和先天性泌尿道畸形的病因学有新的认识。

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.