The analysis of urinary tract formation; a new approach focused on the developmental role of cloaca during embryogenesis

先天性泌尿道疾病在婴儿中常见。此类疾病会出现许多发育异常，例如输尿管积水和肾积水。尽管一些生长因子信号基因的转基因小鼠模型复制了尿液表型，但致病机制仍然不清楚。先前的研究表明，外生殖器和膀胱中的一部分细胞来源于在早期发育阶段接受Hedgehog（Hh）信号的泄殖腔周围间充质细胞。我们推测，这种祖细胞的缺陷，导致泌尿道组织，可能是导致这些疾病的原因。我们的研究确定了泌尿道表型发病的基本胚胎阶段。这些结果表明，Hh-反应性间充质BMP信号传导维持了泄殖腔周围间充质细胞的群体，这对于输尿管和上尿路的发育是必需的。

Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects insuch progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Our study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh-responsive mesenchymal Bmp signaling maintains the population of peri-cloacal mesenchyme cells, which is essential for the development of the ureter and the upper urinary tract.