Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1

Tscharntke, Michael, Pofahl, Ruth, Chrostek-Grashoff, Anna, Smyth, Neil, Niessen, Carien, Niemann, Catherin, Hartwig, Benedikt, Herzog, Volker, Klein, Helmut W., Krieg, Thomas, Brakebusch, Cord and Haase, Ingo (2007) Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1. Journal of Cell Science, 120, (8), 1480-1490. (doi:10.1242/jcs.03426).


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To address the functions of Rac1 in keratinocytes of the basal epidermal layer and in the outer root sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms revealed that in vivo both proliferation of wound-edge keratinocytes and centripetal migration of the neo-epidermis were impaired. Similar results were obtained in mice with an epidermis-specific deletion of Rac1. Primary epidermal keratinocytes that expressed the N17Rac1 transgene were less proliferative than control cells and showed reduced ERK1/2 phosphorylation upon growth factor stimulation. Adhesion, spreading, random migration and closure of scratch wounds in vitro were significantly inhibited on collagen I and, to a lesser extent, on fibronectin. Stroboscopic analysis of cell dynamics (SACED) of N17Rac1 transgenic and control keratinocytes identified decreased lamella-protrusion persistence in connection with increased ruffle frequency as a probable mechanism for the observed impairment of keratinocyte adhesion and migration. We conclude that Rac1 is functionally required for normal epidermal wound healing and, in this context, exerts a dual function – namely the regulation of keratinocyte proliferation and migration.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1242/jcs.03426
ISSNs: 0021-9533 (print)
Related URLs:
Keywords: rac, epidermis, wound healing, keratinocyte, proliferation, migration
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions : University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 55922
Accepted Date and Publication Date:
15 April 2007Published
Date Deposited: 06 Aug 2008
Last Modified: 31 Mar 2016 12:36

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