Increased hedgehog signaling in postnatal kidney results in aberrant activation of nephron developmental programs

摘要: Hedgehog (Hh) is a core signaling pathway implicated in fundamental processes during embryonic kidney development. We previously found that loss-of-function mutations the transcription factor GLIS2, putative vertebrate ortholog of Drosophila Ci, cause nephronophthisis type 7 humans and mice. Kidney tubular cells Glis2-knockout mice acquire mesenchymal phenotype, but cellular mechanisms this transition are unknown. Here, we demonstrate Glis2 functional component Hh necessary to suppress postnatal kidney. In epithelial compartment, opposes Gli1 activity by binding cis-acting regulatory sequences 5′ flanking regions Snai1 Wnt4, thereby inhibiting de-differentiation cells. conclude inhibit maintain mature phenotype adult This first description molecular mechanism links cystic diseases can open new avenues for treatment diverse ciliopathies.