c-Jun is essential for organization of the epidermal leading edge.
The migration of epithelial layers requires specific and coordinated organization of the cells at the leading edge of the sheet. Mice that are conditionally deleted for the c-jun protooncogene in epidermis are born at expected frequencies, but with open eyes and with defects in epidermal wound healing. Keratinocytes lacking c-Jun are unable to migrate or elongate properly in culture at the border of scratch assays. Histological analyses in vitro and in vivo demonstrate an inability to activate EGF receptor at the leading edge of wounds, and we demonstrate that this can be rescued by supplementation with conditioned medium or the EGF receptor ligand HB-EGF. Lack of c-Jun prevents EGF-induced expression of HB-EGF, indicating that c-jun controls formation of the epidermal leading edge through its control of an EGF receptor autocrine loop.
Li
Guochun
G
Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Gustafson-Brown
Cindy
C
Hanks
Steven K
SK
Nason
Katie
K
Arbeit
Jeffrey M
JM
Pogliano
Kit
K
Wisdom
Ronald M
RM
Johnson
Randall S
RS
D000818:Animals; D051379:Mice; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000378:metabolism; D004817:Epidermis / Q000254:growth & development / Q000293:injuries; D066246:ErbB Receptors / Q000378:metabolism; D005143:Eyelids / Q000002:abnormalities / Q000196:embryology; D017353:Gene Deletion; D016758:Genes, jun / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D008822:Mice, Transgenic; D009154:Mutation; D010749:Phosphoprotein Phosphatases; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D054637:Dual-Specificity Phosphatases
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007633:Keratins; D010749:Phosphoprotein Phosphatases; D018809:Proliferating Cell Nuclear Antigen; D018808:Transcription Factor AP-1; C522152:Dusp22 protein, mouse; D054637:Dual-Specificity Phosphatases