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p63 regulates commitment to the prostate cell lineage.

Sabina Signoretti1, Maira M Pires, Meghan Lindauer

  • 1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ssignoretti@partners.org

Proceedings of the National Academy of Sciences of the United States of America
|July 30, 2005
PubMed
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Prostate secretory cells arise from p63-positive basal progenitors. However, urothelial umbrella cells can develop independently of p63, revealing distinct lineage requirements in urinary tract development.

Area of Science:

  • Developmental Biology
  • Urogenital System Development
  • Cell Lineage Specification

Background:

  • The molecular mechanisms governing prostate and urothelial development are poorly understood.
  • This knowledge gap hinders the identification of cell types and molecular events in prostate and bladder cancer.
  • Mice lacking the basal cell marker p63 exhibit epithelial defects, including prostate agenesis and urothelial abnormalities.

Purpose of the Study:

  • To utilize the p63-/- mouse model to define cell lineages within the prostate epithelium and urothelium.
  • To investigate the role of p63 in maintaining prostate cell lineage commitment.
  • To elucidate the developmental independence of urothelial umbrella cells.

Main Methods:

  • Generation of p63-/- mouse chimeras by complementing p63-/- blastocysts with p63+/+ beta-galactosidase (beta-gal)-positive ES cells.

Related Experiment Videos

  • Urogenital sinus transplantation experiments.
  • Analysis of cell lineage contribution and differentiation in chimeric and transplanted tissues.
  • Main Results:

    • Secretory cells of the prostate originate from p63-positive basal progenitor cells.
    • p63 is essential for preventing intestinal differentiation of the urogenital sinus endoderm, maintaining prostate lineage commitment.
    • In the urothelium, umbrella cells can develop and be maintained independently of p63-positive basal and intermediate cells.

    Conclusions:

    • p63 plays a critical role in prostate epithelial development, specifically in basal progenitor cell differentiation into secretory cells.
    • p63 acts as a crucial determinant for prostate lineage, preventing alternative differentiation pathways.
    • Urothelial development, particularly umbrella cell formation, is less dependent on p63 compared to prostate development.