Dissecting Wnt Signaling for Melanocyte Regulation during Wound Healing

Qi Sun, Piul Rabbani, Makoto Takeo, Soung Hoon Lee, Chae Ho Lim, EN Nekema Shandi Noel, M. Mark Taketo, Peggy Myung, Sarah Millar, Mayumi Ito

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Abnormal pigmentation is commonly seen in the wound scar. Despite advancements in the research of wound healing, little is known about the repopulation of melanocytes in the healed skin. Previous studies have shown the capacity of melanocyte stem cells in the hair follicle to contribute skin epidermal melanocytes after injury in mice and humans. Here, we focused on the Wnt pathway, known to be a vital regulator of melanocyte stem cells in efforts to better understand the regulation of follicle-derived epidermal melanocytes during wound healing. We showed that transgenic expression of Wnt inhibitor Dkk1 in melanocytes reduced epidermal melanocytes in the wound scar. Conversely, forced activation of Wnt signaling by genetically stabilizing β-catenin in melanocytes increases epidermal melanocytes. Furthermore, we show that deletion of Wntless (Wls), a gene required for Wnt ligand secretion, within epithelial cells results in failure in activating Wnt signaling in adjacent epidermal melanocytes. These results show the essential function of extrinsic Wnt ligands in initiating Wnt signaling in follicle-derived epidermal melanocytes during wound healing. Collectively, our results suggest the potential for Wnt signal regulation to promote melanocyte regeneration and provide a potential molecular window to promote proper melanocyte regeneration after wounding and in conditions such as vitiligo.

Original languageEnglish
Pages (from-to)1591-1600
Number of pages10
JournalJournal of Investigative Dermatology
Issue number7
StatePublished - Jul 2018
Externally publishedYes


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