The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

摘要: Background Congenital diseases of the urinary tract are frequently observed in infants. Such present a number developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models growth factor signaling genes reproduce phenotypes, pathogenic mechanisms remain obscure. Previous studies suggest that portion cells external genitalia bladder derived from peri-cloacal mesenchymal receive Hedgehog (Hh) early stages. We hypothesized defects progenitor cells, which give rise to tissues, may be cause diseases. Methodology/Principal Findings To elucidate upper malformations, we analyzed series Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydronephrosis phenotypes reduced expression several markers. In addition, suggested Shh modulation at an embryonic stage is responsible for by analyzing conditional mutants. Tissue contribution assays Hh-responsive revealed received Hh signal secreted cloacal epithelium, could contribute ureteral mesenchyme. Gain- loss-of-functional mutants correlation between Bone morphogenetic protein (Bmp) signaling. Finally, ablation Bmp receptor type IA (BmprIA) gene was examined cell lineages. This system thus made it possible analyze primary functions relay. The defective Hh-to-Bmp relay resulted severe with decrease cells. Conclusions/Significance This study identified essential stages pathogenesis phenotypes. These results maintains population mesenchyme development ureter tract.