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PMID:20643356

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Citation

Caddy, J, Wilanowski, T, Darido, C, Dworkin, S, Ting, SB, Zhao, Q, Rank, G, Auden, A, Srivastava, S, Papenfuss, TA, Murdoch, JN, Humbert, PO, Parekh, V, Boulos, N, Weber, T, Zuo, J, Cunningham, JM and Jane, SM (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev. Cell 19:138-47

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 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.

Links

PubMed PMC2965174 Online version:10.1016/j.devcel.2010.06.008

Keywords

Actins/metabolism; Animals; Cell Polarity/physiology; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Epidermis/embryology; Epidermis/injuries; Epidermis/physiology; Female; 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; Mutation; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/physiology; Pregnancy; Signal Transduction; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology; Wound Healing/genetics; Wound Healing/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CELR1

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1918711
MGI:MGI:2135272
MGI:MGI:2145950
MGI:MGI:2655333

P

  • occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0001736: establishment of planar polarity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2135272

P

  • occurs_in:(EMAPA:19061)

Seeded From UniProt

complete

MOUSE:GRHL3

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:1925912)

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2684328

P

  • regulates_o_occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0043547: positive regulation of GTPase activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1925912

P

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1100883
MGI:MGI:1918711
MGI:MGI:2135272
MGI:MGI:2145950

P

  • occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0090179: planar cell polarity pathway involved in neural tube closure

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2135272

P

  • occurs_in:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:GRHL3

acts_upstream_of_or_within

GO:0090103: cochlea morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2135272

P

Seeded From UniProt

complete

MOUSE:SCRIB

acts_upstream_of_or_within

GO:0001843: neural tube closure

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1889322

P

Seeded From UniProt

complete

MOUSE:SCRIB

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1100883
MGI:MGI:1918711
MGI:MGI:2135272
MGI:MGI:2655333

P

  • occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:PTK7

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1100883
MGI:MGI:2135272
MGI:MGI:2145950
MGI:MGI:2655333

P

  • occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:ARHGJ

acts_upstream_of_or_within

GO:0043547: positive regulation of GTPase activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2655333

P

Seeded From UniProt

complete

MOUSE:ARHGJ

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ARHGJ

acts_upstream_of_or_within

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q8TE85

P

Seeded From UniProt

complete

HUMAN:GRHL3

acts_upstream_of_or_within

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q8IW93

P

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0001736: establishment of planar polarity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2655333

P

  • occurs_in:(EMAPA:19061)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1100883
MGI:MGI:1918711
MGI:MGI:2145950
MGI:MGI:2655333

P

  • occurs_in:(EMAPA:17528)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0090179: planar cell polarity pathway involved in neural tube closure

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2655333

P

  • occurs_in:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0090103: cochlea morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2655333

P

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1918711
MGI:MGI:2135272
MGI:MGI:2145950
MGI:MGI:2655333

P

occurs_in:(EMAPA:17528)

Seeded From UniProt

complete


See also

References

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