The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (ΔN) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and prostate glands.
Although p63-expressing cells are proposed to be the stem cells of the developing prostate epithelium and bladder urothelium, cell lineages in these endoderm-derived epithelia remain highly controversial, and rigorous lineage tracing studies are warranted. Here, we generated knock-in mice expressing Cre recombinase (Cre) under the control of the endogenous ΔNp63 promoter. Heterozygote ΔNp63+/Cre mice were phenotypically normal and fertile. Cre-mediated recombination in ΔNp63+/Cre;ROSA26EYFP reporter mice faithfully recapitulated the pattern of ΔNp63 expression and were useful for genetic lineage tracing of ΔNp63-expressing cells of the caudal endoderm in vivo. We found that ΔNp63-positive cells of the urogenital sinus generated all epithelial lineages of the prostate and bladder, indicating that these cells represent the stem/progenitor cells of those epithelia during development. We also observed ΔNp63 expression in caudal gut endoderm and the contribution of ΔNp63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon.
Written by:
Pignon JC, Grisanzio C, Geng Y, Song J, Shivdasani RA, Signoretti S. Are you the author?
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Reference: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8105-10.
doi: 10.1073/pnas.1221216110
PubMed Abstract
PMID: 23620512
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