Control of Lineage Decisions in the Embryonic Kidney by Hedgehog Signalling

Foxd1-expressing cells give rise to stromal components in the mammalian embryonic kidney, and are the major source of myofibroblasts during renal fibrosis. The signalling pathways involved in segregation of the stromal and nephrogenic lineages from their common precursor cells is not fully understood. Previous studies in the Rosenblum lab have shown the role of HH signaling in expansion of cortical stromal gene expression and ureteropelvic junction development. I present a stage-specific role for HH signalling in early renal precursors expressing Sall1 and Osr1 in promoting stromal cell specification without affecting the nephrogenic lineage. Temporal deletion of Ptc1 in Sall1+ and Osr1+ cells results in an early increase in stromal cells, disorganization of the cortical stroma, medullary localization of cortical stromal cells, decreased nephron number, and no change in cell proliferation. Mutant kidneys exhibit UPJ obstruction at birth caused by ectopic cortical stromal cells in an activated state of HH signalling.M.Sc.2017-11-30 00:00:0