Epidermal Wound Repair Is Regulated by the Planar Cell Polarity Signaling Pathway

• Published in: Developmental cell Vol. 19; no. 1; pp. 138 - 147
• Main Authors: Caddy, Jacinta, Wilanowski, Tomasz, Darido, Charbel, Dworkin, Sebastian, Ting, Stephen B., Zhao, Quan, Rank, Gerhard, Auden, Alana, Srivastava, Seema, Papenfuss, Tony A., Murdoch, Jennifer N., Humbert, Patrick O., Boulos, Nidal, Weber, Thomas, Zuo, Jian, Cunningham, John M., Jane, Stephen M.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 20.07.2010; Cell Press
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell Polarity - physiology; CELLBIO; DEVBIO; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Epidermis - embryology; Epidermis - injuries; Epidermis - physiology; Female; Fundamental and applied biological sciences. Psychology; Guanine Nucleotide Exchange Factors - deficiency; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - physiology; Keratinocytes - cytology; Keratinocytes - physiology; Mice; Mice, Knockout; Mice, Mutant Strains; Models, Biological; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Pregnancy; Rho Guanine Nucleotide Exchange Factors; Signal Transduction; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; Wound Healing - genetics; Wound Healing - physiology; CELLBIO; DEVBIO; Development; Signal transduction; Repair; Wound; Cellular polarity; Cell signaling
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2010.06.008

The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3−/− mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. [Display omitted] ► Grhl3 is a component of the PCP signaling pathway ► Grhl3 acts in this pathway through the RhoA activator, RhoGEF19 ► PCP signaling regulates mammalian embryonic epidermal wound repair