Research article

Wnt signaling induces epithelial differentiation during cutaneous wound healing

Carrie Fathke¹ , Lynne Wilson¹ , Kavita Shah² , Brian Kim¹ , Anne Hocking¹ , Randall Moon² and Frank Isik¹

¹Department of Surgery, University of Washington School of Medicine, Seattle, WA 98195, USA

²Howard Hughes Medical Institute/Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA

author email corresponding author email

BMC Cell Biology 2006, 7:4doi:10.1186/1471-2121-7-4

Published:	20 January 2006

Abstract

Background

Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair.

Results

We determined that the expression of Wnt ligands that typically signal via the beta-catenin-independent pathway is up-regulated in the wound while the beta-catenin-dependent Wnt signaling is activated in the hair follicles adjacent to the wound edge. Ectopic activation of beta-catenin-dependent Wnt signaling with lithium chloride in the wound resulted in epithelial cysts and occasional rudimentary hair follicle structures within the epidermis. In contrast, forced expression of Wnt-5a in the deeper wound induced changes in the interfollicular epithelium mimicking regeneration, including formation of epithelia-lined cysts in the wound dermis, rudimentary hair follicles and sebaceous glands, without formation of tumors.

Conclusion

These findings suggest that adult interfollicular epithelium is capable of responding to Wnt morphogenic signals necessary for restoring epithelial tissue patterning in the skin during wound repair.