Amphibians and birds excrete waste products through the cloaca, an endodermally lined chamber. In mammals, the cloaca gives rise to some of the more specialised structures of the urogenital and reproductive organs. Quite how the cloaca gives rise to these crucial organs has remained elusive and understudied. Now, on , Haraguchi et al. shed much-needed light on this developmental process. They reveal that Shh and Gli mutant mice display hypoplasia of the external genitalia, internal urethra and bladder, indicating a requirement for Hh signalling in their development. Using the Gli1-CreERT2mouse, the authors have fate mapped Hh-responsive mesenchyme and found that the bladder mesenchyme and external genitalia derive from Shh-responsive peri-cloacal mesenchyme, revealing how the coordination of urogenital formation is regulated by Hh signalling. The precise source, targets and ligands required for urogenital and reproductive development require further investigation, especially because future treatments of congenital urogenitary defects that are less invasive than reconstructive surgery may stem from these and future findings.
