Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2041-2050
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number9
DOIs
Publication statusPublished - 2018 Sep 1

Fingerprint

Mammals
Hair Follicle
Chemical activation
Binding Sites
Wounds and Injuries
Regeneration
Epithelium
Mesoderm
Epidermis
Wound Healing
Hair
Mental Competency
Cicatrix

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Hughes, M. W., Jiang, T. X., Plikus, M. V., Guerrero-Juarez, C. F., Lin, C. H., Schafer, C., ... Chuong, C. M. (2018). Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis. Journal of Investigative Dermatology, 138(9), 2041-2050. https://doi.org/10.1016/j.jid.2018.02.043
Hughes, Michael Warren ; Jiang, Ting Xin ; Plikus, Maksim V. ; Guerrero-Juarez, Christian Fernando ; Lin, Chien Hong ; Schafer, Christopher ; Maxson, Robert ; Widelitz, Randall B. ; Chuong, Cheng Ming. / Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 9. pp. 2041-2050.
@article{eaaf1ffa1e4d4dd09f989f34e104ca0b,
title = "Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis",
abstract = "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.",
author = "Hughes, {Michael Warren} and Jiang, {Ting Xin} and Plikus, {Maksim V.} and Guerrero-Juarez, {Christian Fernando} and Lin, {Chien Hong} and Christopher Schafer and Robert Maxson and Widelitz, {Randall B.} and Chuong, {Cheng Ming}",
year = "2018",
month = "9",
day = "1",
doi = "10.1016/j.jid.2018.02.043",
language = "English",
volume = "138",
pages = "2041--2050",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "9",

}

Hughes, MW, Jiang, TX, Plikus, MV, Guerrero-Juarez, CF, Lin, CH, Schafer, C, Maxson, R, Widelitz, RB & Chuong, CM 2018, 'Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis', Journal of Investigative Dermatology, vol. 138, no. 9, pp. 2041-2050. https://doi.org/10.1016/j.jid.2018.02.043

Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis. / Hughes, Michael Warren; Jiang, Ting Xin; Plikus, Maksim V.; Guerrero-Juarez, Christian Fernando; Lin, Chien Hong; Schafer, Christopher; Maxson, Robert; Widelitz, Randall B.; Chuong, Cheng Ming.

In: Journal of Investigative Dermatology, Vol. 138, No. 9, 01.09.2018, p. 2041-2050.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis

AU - Hughes, Michael Warren

AU - Jiang, Ting Xin

AU - Plikus, Maksim V.

AU - Guerrero-Juarez, Christian Fernando

AU - Lin, Chien Hong

AU - Schafer, Christopher

AU - Maxson, Robert

AU - Widelitz, Randall B.

AU - Chuong, Cheng Ming

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048127611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048127611&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2018.02.043

DO - 10.1016/j.jid.2018.02.043

M3 - Article

C2 - 29577917

AN - SCOPUS:85048127611

VL - 138

SP - 2041

EP - 2050

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 9

ER -