Epidermal Wound Repair Is Regulated by the Planar Cell Polarity Signaling Pathway
| Autor: | Charbel Darido, Jennifer N. Murdoch, Vishwas Parekh, Sebastian Dworkin, Stephen B. Ting, Gerhard Rank, Thomas Weber, Nidal Boulos, Tony Papenfuss, Jacinta Caddy, Stephen M. Jane, Alana Auden, Seema Srivastava, John M. Cunningham, Jian Zuo, Tomasz Wilanowski, Quan Zhao, Patrick O. Humbert |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Keratinocytes
Cell signaling RHOA Cellular polarity Xenopus Nerve Tissue Proteins DEVBIO Models Biological Article General Biochemistry Genetics and Molecular Biology Mice Pregnancy Planar cell polarity Cell polarity medicine Animals Guanine Nucleotide Exchange Factors book Molecular Biology Transcription factor Mice Knockout Wound Healing integumentary system biology Developmental cell Neural tube Cell Polarity Cell Biology biology.organism_classification Actins Mice Mutant Strains Cell biology DNA-Binding Proteins medicine.anatomical_structure Mutation biology.protein book.journal Female CELLBIO Signal transduction Epidermis Wound healing Rho Guanine Nucleotide Exchange Factors Signal Transduction Transcription Factors Developmental Biology |
| Zdroj: | Developmental Cell. 19:138-147 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2010.06.008 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|