Epidermal Wound Repair Is Regulated by the Planar Cell Polarity Signaling Pathway
- Author(s)
- Caddy, J; Wilanowski, T; Darido, C; Dworkin, S; Ting, SB; Zhao, Q; Rank, G; Auden, A; Srivastava, S; Papenfuss, TA; Murdoch, JN; Humbert, PO; Boulos, N; Weber, T; Zuo, JA; Cunningham, JM; Jane, SM;
- Details
- Publication Year 2010-07-20,Volume 19,Issue #1,Page 138-147
- Journal Title
- DEVELOPMENTAL CELL
- Publication Type
- Journal Article
- Abstract
- 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 Vang12, 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.
- Publisher
- CELL PRESS
- Keywords
- NEURAL-TUBE DEFECTS; DEVELOPMENTAL TRANSCRIPTION FACTORS; TRIPLE-HELIX REPEAT; RHO-FAMILY GTPASES; GRAINY-HEAD; XENOPUS GASTRULATION; LEADING-EDGE; PCP PATHWAY; LOOP-TAIL; DROSOPHILA
- Publisher's Version
- https://doi.org/10.1016/j.devcel.2010.06.008
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-07-20 12:00:00