Institute of Molecular Biology, Hannover Medical School, 30625 Hannover, Germany.
Colon Cancer Program, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto University, Yoshida-Honmachi, Sakyo, Kyoto 606-8501, Japan.
Development. 2023 Mar 15;150(6). doi: 10.1242/dev.201048. Epub 2023 Mar 23.
The murine kidney and ureter develop in a regionalized fashion from the ureteric bud and its surrounding mesenchyme. Whereas the factors that establish the metanephric cell lineages have been well characterized, much less is known about the molecular cues that specify the ureter. Here, we have identified a crucial patterning function in this process for Tbx18, a T-box transcription factor gene specifically expressed in the mesenchymal primordium of the ureter. Using misexpression and loss-of-function mice combined with molecular profiling approaches, we show that Tbx18 is required and sufficient to repress metanephric mesenchymal gene programs. We identify Wt1 as a functional target of TBX18. Our work suggests that TBX18 acts as a permissive factor in ureter specification by generating a mesenchymal domain around the distal ureteric bud where SHH and BMP4 signaling can occur.
鼠肾和输尿管从输尿管芽及其周围的间充质以区域化的方式发育。虽然已经很好地描述了确定后肾细胞谱系的因素，但对于指定输尿管的分子线索知之甚少。在这里，我们确定了 Tbx18 在这个过程中的关键模式形成功能，Tbx18 是一种 T 盒转录因子基因，特异性表达在输尿管的间充质原基中。我们使用过表达和功能丧失小鼠以及分子分析方法，表明 Tbx18 是抑制后肾间充质基因程序所必需和充分的。我们确定 Wt1 是 TBX18 的功能靶点。我们的工作表明，TBX18 通过在远端输尿管芽周围产生一个间充质域来作为输尿管指定的许可因子，在这个域中可以发生 SHH 和 BMP4 信号。
