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Epidermal wound repair is regulated by the planar cell polarity signaling pathway

Jacinta Caddy1, Tomasz Wilanowski, Charbel Darido

  • 1Rotary Bone Marrow Research Laboratories, Parkville, Victoria 3050, Australia.

Developmental Cell
|July 21, 2010
PubMed

Insights

The planar cell polarity (PCP) pathway is crucial for skin repair. This study identifies GRHL3 as a key regulator of PCP signaling, impacting cell movement and wound healing.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • The planar cell polarity (PCP) pathway governs cell orientation and movement in various developmental processes.
  • Key PCP pathway genes include Vangl2, Celsr1, PTK7, and Scrb1.
  • The transcription factor Grhl3's role in PCP signaling was previously unknown.

Purpose of the Study:

  • To investigate the role of the PCP pathway in epidermal wound repair.
  • To identify novel regulators of PCP signaling in skin.
  • To elucidate the function of Grhl3 in the context of PCP signaling and wound healing.

Main Methods:

  • Genetic analysis of mice with mutations in PCP genes and Grhl3.
  • Phylogenetic analysis, ChIP, and gene expression studies in Grhl3 knockout mice.
  • In vitro knockdown and rescue experiments in keratinocytes.

Main Results:

  • Mutations in PCP genes and Grhl3 led to impaired wound healing, neural tube defects, and cochlear polarity issues.
  • RhoGEF19 was identified as a direct transcriptional target of GRHL3.
  • Knockdown of Grhl3 or RhoGEF19 in keratinocytes disrupted actin polymerization, cell polarity, and wound healing, which was rescued by RhoGEF19 re-expression.

Conclusions:

  • Grhl3 plays a significant role in regulating PCP signaling.
  • The PCP pathway is broadly implicated in epidermal repair processes.
  • RhoGEF19 is a critical mediator of Grhl3's function in cell polarity and wound healing.

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