Format

Send to

Choose Destination
Dev Cell. 2012 Sep 11;23(3):637-51. doi: 10.1016/j.devcel.2012.07.008. Epub 2012 Aug 16.

Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.

Author information

1
Division of Pediatric Urology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. joo-seop.park@cchmc.org

Abstract

A balance between Six2-dependent self-renewal and canonical Wnt signaling-directed commitment regulates mammalian nephrogenesis. Intersectional studies using chromatin immunoprecipitation and transcriptional profiling identified direct target genes shared by each pathway within nephron progenitors. Wnt4 and Fgf8 are essential for progenitor commitment; cis-regulatory modules flanking each gene are cobound by Six2 and β-catenin and are dependent on conserved Lef/Tcf binding sites for activity. In vitro and in vivo analyses suggest that Six2 and Lef/Tcf factors form a regulatory complex that promotes progenitor maintenance while entry of β-catenin into this complex promotes nephrogenesis. Alternative transcriptional responses associated with Six2 and β-catenin cobinding events occur through non-Lef/Tcf DNA binding mechanisms, highlighting the regulatory complexity downstream of Wnt signaling in the developing mammalian kidney.

PMID:
22902740
PMCID:
PMC3892952
DOI:
10.1016/j.devcel.2012.07.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center