Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis

Michael W. Hughes, Ting Xin Jiang, Maksim V. Plikus, Christian Fernando Guerrero-Juarez, Chien Hong Lin, Christopher Schafer, Robert Maxson, Randall B. Widelitz, Cheng Ming Chuong

研究成果: Article同行評審

8 引文 斯高帕斯(Scopus)


Cutaneous wounds in adult mammals typically heal by scarring. However, large full-thickness wounds undergo wound-induced hair follicle neogenesis (WIHN), a form of regeneration. Here, we show that WIHN requires transient expression of epidermal Msx2 in two phases: the wound margin early and the wound center late. Msx2 expression is present in the migrating epithelium during early wound healing and then presents in the epithelium and mesenchyme later in the wound center. WIHN is abrogated in germline and epithelial-specific Msx2 mutant mice. Unlike the full-length Msx2 promoter, a minimal Msx2 promoter fails activation in the wound center, suggesting complex regulation of Msx2 expression. The Msx2 promoter binding sites include Tcf/Lef, Jun/Creb, Pax3, and three SMAD sites. However, basal epithelial-induced BMP suppression by noggin overexpression did not affect WIHN. We propose that Msx2 signaling is required for the epidermis to acquire spatiotemporal competence during WIHN. Topologically, hair regeneration dominates in the wound center, coinciding with late Msx2 expression. Together, these results suggest that intrinsic Msx2 expression supports epithelial competency during hair follicle neogenesis. This work provides insight into endogenous mechanisms modulating competency of adult epidermal progenitors for mammalian ectodermal appendage neogenesis, and offers the target Msx2 for future regeneration-promoting therapies.

頁(從 - 到)2041-2050
期刊Journal of Investigative Dermatology
出版狀態Published - 2018 九月

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 皮膚科
  • 細胞生物學


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