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

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 beta-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How beta-catenin stimulated these two distinct programs was unclear. Here, we show that beta-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program. Although in multiple contexts Myc is a target of beta-catenin, our characterization of a cell type-specific enhancer for the Wnt9b/beta-catenin target gene Fam19a5 shows that Myc and beta-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/beta-catenin progenitor renewal target assessed as well as for proper nephron endowment in vivo. This study suggests that, within the developing kidney, tissue-specific beta-catenin activity is regulated by cooperation with cell type-specific transcription factors. This finding not only provides insight into the regulation of beta-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 beta-catenin are co-expressed.