DNP63 regulates epithelial stratification and differentiation in the murine ureter

At E15.5, i.e. shortly after the onset of DNP63 expression in the ureter, epithelial proliferation and cell division planes were unaffected. Transcriptional profiling revealed that DNp63 is required for the expression of genes that regulate epithelial stratification, cell adhesion and division. DNP63 is also responsible for repression of Ihh, precluding premature formation of the lamina propria.

Analysis of mutant ureters at postnatal stages revealed a progressive reconstitution of the normal urothelial cytoarchitecture, suggesting that DNP63+ epithelial progenitors that have escaped recombination, undergo rapid proliferative expansion and differentiation into I and B cells. Our results suggest that a conserved DNP63 gene regulatory module is responsible for epithelial stratification, expansion of basal and intermediate cells, and correct differentiation of superficial cells in the murine ureter.