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Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
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Published on: December 14, 2015

p63 induces key target genes required for epidermal morphogenesis.

Maranke I Koster1, Daisy Dai, Barbara Marinari

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 16, 2007
PubMed
Summary

DeltaNp63 proteins are crucial for skin development, maintaining the basement membrane, and keratinocyte differentiation. Their function is vital for epidermal morphogenesis and homeostasis.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • p63 transcription factors are essential for stratified epithelia, appendages, and limb development.
  • DeltaNp63 isoforms are expressed in the epidermis but their function is not well understood.

Purpose of the Study:

  • To investigate the role of DeltaNp63 proteins in epidermal development and homeostasis.
  • To identify target genes of DeltaNp63alpha involved in epidermal morphogenesis.

Main Methods:

  • Utilized an epidermal-specific inducible knockdown mouse model.
  • Analyzed basement membrane integrity and keratinocyte terminal differentiation.
  • Identified DeltaNp63alpha target genes Fras1 and IkappaB kinase-alpha.

Main Results:

  • DeltaNp63 proteins are essential for maintaining basement membrane integrity.
  • DeltaNp63 proteins are required for keratinocyte terminal differentiation.
  • Fras1 and IkappaB kinase-alpha were identified as key target genes mediating these processes.

Conclusions:

  • DeltaNp63alpha induces Fras1 for basement membrane integrity.
  • DeltaNp63alpha induces IkappaB kinase-alpha to initiate epidermal terminal differentiation.
  • These findings elucidate DeltaNp63alpha's role in epidermal morphogenesis and homeostasis, potentially informing p63 mutation-related disorders.