Myc cooperates with ?-catenin to drive gene expression in nephron progenitor cells.

ABSTRACT: For organs to achieve their proper size, the processes of stem cell renewal and differentiation must be tightly regulated. We previously showed that in the developing kidney, Wnt9b regulates distinct ?-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How ?-catenin stimulated these two distinct programs was unclear. Here, we show that ?-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program. Although in multiple contexts Myc is a target of ?-catenin, our characterization of a cell type-specific enhancer for the Wnt9b/?-catenin target gene Fam19a5 shows that Myc and ?-catenin cooperate to activate gene expression controlled by this element. This appears to be a more general phenomenon as we find that Myc is required for the expression of every Wnt9b/?-catenin progenitor renewal target assessed as well as for proper nephron endowment in vivo This study suggests that, within the developing kidney, tissue-specific ?-catenin activity is regulated by cooperation with cell type-specific transcription factors. This finding not only provides insight into the regulation of ?-catenin target genes in the developing kidney, but will also advance our understanding of progenitor cell renewal in other cell types/organ systems in which Myc and ?-catenin are co-expressed.

SUBMITTER: Pan X 

PROVIDER: S-EPMC5719246 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature