ΔNP63 regulates epithelial stratification and differentiation in the murine ureter.

Authors

Fairouz Qasrawi, Florian Bergmann, Philipp Straube, Hauke Thiesler, Herbert Hildebrandt, Satrajit Sinha, Elsa R Flores, Mark-Oliver Trowe, Carsten Rudat, Andreas Kispert

Published in

American journal of physiology. Renal physiology. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

The urothelium is a stratified epithelium that lines the inner surfaces of organs in the urinary drainage system. It has a layered composition of basal, intermediate, and large superficial cells. The process, by which this cytoarchitecture develops from uncommitted precursor cells is not well understood. In this study, we analyzed the cellular and molecular functions of the transcription factor ΔNP63 in urothelial development in the murine ureter. ΔNP63 expression begins in epithelial progenitors of this organ at embryonic day (E)14.5 and is confined to basal and intermediate cells from late fetal stages onwards. In mice with a conditional loss of ΔNp63 in the epithelial progenitors, the ureteric urothelium presented as a folded monolayer composed predominantly of partially differentiated superficial cells around birth. At E15.5, the proliferation and division planes of epithelial cells remained unaffected. However, genes essential for cell adhesion and division in other epithelial stratification programs were downregulated, as were genes involved in B and I cell differentiation. In contrast, Ihh expression in the epithelium increased concomitantly with the premature formation of the lamina propria. Our results suggest that a conserved ΔNP63 gene regulatory module is responsible for epithelial stratification and the differentiation of basal and intermediate cells, as well as the timely differentiation of the lamina propria in fetal ureter development. The urothelial cytoarchitecture was progressively reconstituted in ΔNp63-deficient ureters after birth. This suggests that a few NP63⁺ epithelial progenitors, which have escaped recombination, can undergo rapid proliferative expansion and differentiation into I and B cells.

PMID:
42412652
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.

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