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Nat Commun. 2018 Nov 21;9(1):4903. doi: 10.1038/s41467-018-07142-9.

Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing.

Author information

1
The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA.
2
Department of Dermatology and Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
3
Department of Developmental and Cell Biology, Irvine, Sue and Bill Gross Stem Cell Center, University of California, Irvine, CA, 92617, USA.
4
Centre for Cancer Research, Hudson Institute for Medical Research and Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, 3816, Australia.
5
Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, Esophageal Diseases Center, Medical Service, VA North Texas Health Care System, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
6
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
7
Division of Experimental Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
8
Departments of Dermatology and Pathology, School of Medicine, Yale University, New Haven, CT, 06520, USA.
9
The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA. mayumi.ito@nyumc.org.

Abstract

Mammalian wounds typically heal by fibrotic repair without hair follicle (HF) regeneration. Fibrosis and regeneration are currently considered the opposite end of wound healing. This study sought to determine if scar could be remodeled to promote healing with HF regeneration. Here, we identify that activation of the Sonic hedgehog (Shh) pathway reinstalls a regenerative dermal niche, called dermal papilla, which is required and sufficient for HF neogenesis (HFN). Epidermal Shh overexpression or constitutive Smoothened dermal activation results in extensive HFN in wounds that otherwise end in scarring. While long-term Wnt activation is associated with fibrosis, Shh signal activation in Wnt active cells promotes the dermal papilla fate in scarring wounds. These studies demonstrate that mechanisms of scarring and regeneration are not distant from one another and that wound repair can be redirected to promote regeneration following injury by modifying a key dermal signal.

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