Interferon regulatory factor 6 regulates keratinocyte migration.
Interferon regulatory factor 6 (Irf6) regulates keratinocyte proliferation and differentiation. In this study, we tested the hypothesis that Irf6 regulates cellular migration and adhesion. Irf6-deficient embryos at 10.5 days post-conception failed to close their wound compared with wild-type embryos. In vitro, Irf6-deficient murine embryonic keratinocytes were delayed in closing a scratch wound. Live imaging of the scratch showed deficient directional migration and reduced speed in cells lacking Irf6. To understand the underlying molecular mechanisms, cell-cell and cell-matrix adhesions were investigated. We show that wild-type and Irf6-deficient keratinocytes adhere similarly to all matrices after 60 min. However, Irf6-deficient keratinocytes were consistently larger and more spread, a phenotype that persisted during the scratch-healing process. Interestingly, Irf6-deficient keratinocytes exhibited an increased network of stress fibers and active RhoA compared with that observed in wild-type keratinocytes. Blocking ROCK, a downstream effector of RhoA, rescued the delay in closing scratch wounds. The expression of Arhgap29, a Rho GTPase-activating protein, was reduced in Irf6-deficient keratinocytes. Taken together, these data suggest that Irf6 functions through the RhoA pathway to regulate cellular migration.
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA.
Leah C
LC
Biggs
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA.
Rachelle L
RL
Naridze
Department of Biochemistry, The University of Iowa, Iowa City, IA 52242, USA.
Kris A
KA
DeMali
Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
Daniel F
DF
Lusche
Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
Spencer
S
Kuhl
Developmental Studies Hybridoma Bank, Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
David R
DR
Soll
Departments of Microbiology and Molecular Genetics and of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA.
Brian C
BC
Schutte
Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA martine-dunnwald@uiowa.edu.
Martine
M
Dunnwald
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D046149:Embryo Culture Techniques; D005260:Female; D050835:Interferon Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
C528250:IRF6 protein, mouse; D050835:Interferon Regulatory Factors; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
Interferon regulatory factor 6; Keratinocytes; Migration