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 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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Park JS,Ma W,O'Brien LL,Chung E,Guo JJ,Cheng JG,Valerius MT,McMahon JA,Wong WH,McMahon AP

doi

10.1016/j.devcel.2012.07.008

subject

Has Abstract

pub_date

2012-09-11 00:00:00

pages

637-51

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(12)00327-9

journal_volume

23

pub_type

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