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Updated: Jun 25, 2026

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
Published on: December 14, 2015
Perp is a p63-regulated gene essential for epithelial integrity
Rebecca A Ihrie1, Michelle R Marques, Bichchau T Nguyen
1Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Insights
Perp is a direct target of p63, crucial for stratified epithelial development. Perp-deficient mice exhibit skin blistering, revealing Perp’s essential role in maintaining epithelial adhesion and tissue integrity.
Area of Science:
- Developmental Biology
- Epithelial Biology
- Molecular Biology
Background:
- p63 is a master regulator of stratified epithelial development.
- Perp, a tetraspan membrane protein, was previously identified as a p53 target involved in apoptosis.
Purpose of the Study:
- To investigate the role of Perp as a direct target of p63 in epithelial development.
- To elucidate Perp's function in vivo during embryogenesis and its contribution to epithelial integrity.
Main Methods:
- Analysis of Perp expression during embryogenesis.
- Generation and characterization of Perp knockout (Perp-/-) mice.
- Histological examination of skin and epithelial tissues.
- Localization studies of Perp protein at desmosomes.
Main Results:
- Perp expression is dependent on p63 during embryogenesis.
- Perp-/- mice display severe blistering in stratified epithelia due to compromised adhesion.
- Perp localizes to desmosomes and is essential for their stable assembly.
- Perp deficiency leads to structural defects in desmosomes and impaired tissue integrity.
Conclusions:
- Perp is the first identified direct target of p63 involved in mediating stratified epithelial development.
- Perp plays a critical role in an epithelial adhesion subprogram essential for tissue integrity and homeostasis.
- These findings establish Perp as a key effector in the p63 developmental pathway.
Abstract:
p63 is a master regulator of stratified epithelial development that is both necessary and sufficient for specifying this multifaceted program. We show here that Perp, a tetraspan membrane protein originally identified as an apoptosis-associated target of the p53 tumor suppressor, is the first direct target of p63 clearly involved in mediating this developmental program in vivo. During embryogenesis, Perp is expressed in an epithelial pattern, and its expression depends on p63. Perp-/- mice die postnatally, with dramatic blistering in stratified epithelia symptomatic of compromised adhesion. Perp localizes specifically to desmosomes, adhesion junctions important for tissue integrity, and numerous structural defects in desmosomes are observed in Perp-deficient skin, suggesting a role for Perp in promoting the stable assembly of desmosomal adhesive complexes. These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis.
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