Unknown

Dataset Information

0

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


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 ?-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 ?-catenin into this complex promotes nephrogenesis. Alternative transcriptional responses associated with Six2 and ?-catenin cobinding events occur through non-Lef/Tcf DNA binding mechanisms, highlighting the regulatory complexity downstream of Wnt signaling in the developing mammalian kidney.

SUBMITTER: Park JS 

PROVIDER: S-EPMC3892952 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Park Joo-Seop JS   Ma Wenxiu W   O'Brien Lori L LL   Chung Eunah E   Guo Jin-Jin JJ   Cheng Jr-Gang JG   Valerius M Todd MT   McMahon Jill A JA   Wong Wing Hung WH   McMahon Andrew P AP  

Developmental cell 20120816 3


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  ...[more]

Similar Datasets

| S-EPMC4282136 | biostudies-literature
| S-EPMC3210493 | biostudies-literature
2016-04-14 | E-GEOD-79024 | biostudies-arrayexpress
| S-EPMC7032615 | biostudies-literature
| S-EPMC6361385 | biostudies-literature
2012-09-11 | E-GEOD-39837 | biostudies-arrayexpress
| S-EPMC10690271 | biostudies-literature
| S-EPMC9257825 | biostudies-literature
2014-03-24 | E-GEOD-45845 | biostudies-arrayexpress
| S-EPMC6970988 | biostudies-literature