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 β-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How β-catenin stimulated these two distinct programs was unclear. Here, we show that β-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program. Although in multiple contexts Myc is a target of β-catenin, our characterization of a cell type-specific enhancer for the Wnt9b/β-catenin target gene Fam19a5 shows that Myc and β-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/β-catenin progenitor renewal target assessed as well as for proper nephron endowment in vivo This study suggests that, within the developing kidney, tissue-specific β-catenin activity is regulated by cooperation with cell type-specific transcription factors. This finding not only provides insight into the regulation of β-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 β-catenin are co-expressed.
Keywords: Fam19a5; Mouse; Myc; Nephron progenitors; Stem cells; Wnt; β-Catenin.
© 2017. Published by The Company of Biologists Ltd.