Disruption of renal development in humans with Pallister-Hall Syndrome and truncating GLI3 mutations [33] and mice with elevated levels of GLI3 repressor [9], [10] provides compelling evidence in favor of a critical role for GLI3-dependent signaling during mesenchymal-epithelial interactions during early stages of metanephric development. The gene discussed is GLI3; the disease is Pallister-Hall syndrome.