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 Celljournal_title
Developmental cellauthors
Park JS,Ma W,O'Brien LL,Chung E,Guo JJ,Cheng JG,Valerius MT,McMahon JA,Wong WH,McMahon APdoi
10.1016/j.devcel.2012.07.008subject
Has Abstractpub_date
2012-09-11 00:00:00pages
637-51issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(12)00327-9journal_volume
23pub_type
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