Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog
Open accessAbstract
Hair follicles form in prenatal skin and mature in the postnatal period, establishing a growth cycle in 3 phases: telogen (resting), anagen (growth), and catagen (regression). Based on the knowledge that Sonic hedgehog (Shh) expression is necessary for the embryonic development of hair follicles, and that anagen in the postnatal cycling follicle has morphologic similarities to the epithelial invagination process in embryonic skin, we hypothesized that localized, but transient, enhanced expression of the Shh gene in postnatal skin would accelerate initiation of anagen in the hair follicle cycle, with concomitant accelerated hair growth. To assess this concept, an E1(-) adenovirus vector, AdShh, was used to transfer the murine Shh cDNA to skin of postnatal day 19 C57BL/6 mice. The treated skin showed increased mRNA expression of Shh, Patched (the Shh receptor), and Gli1 (a transcription factor in the Shh pathway). In mice receiving AdShh, but not in controls, acceleration into anagen was evident, since hair follicle size and melanogenesis increased and the hair-specific keratin ghHb-1 and the melanin synthesis-related tyrosinase mRNAs accumulated. Finally, C57BL/6 mice showed marked acceleration of the onset of new hair growth in the region of AdShh administration to skin 2 weeks after treatment, but not in control vector-treated or untreated areas. After 6 months, AdShh-treated skin showed normal hair and normal skin morphology. Together, these observations are consistent with the concept that upregulation of Shh activity in postnatal skin functions as a biologic switch that induces resting hair follicles to enter anagen with consequent hair growth.
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Induction of anagen can occur through signals from the dermal papilla.
“While induction of anagen can occur through signals from the dermal papilla30, the lack of detectable levels of TERT mRNA in the dermal papilla (Fig. 1h) makes it unlikely in this case.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [30]
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Molecular Mechanisms Regulating Hair Follicle Development
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- Authors
- Sato, N., Leopold, P. L., & Crystal, R. G.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Crystal, Ronald G.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-10-01
- Volume
- 104
- Issue
- 7
- Pages
- 855-864
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408560
- OpenAlex
- W2033414562
- Cited by
- 253
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 12 · 2016: 6 · 2015: 2 · 2014: 9 · 2013: 10 · 2012: 10
- FWCI
- 19.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harvard University
- Johns Hopkins University
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- Sonic hedgehog, hair follicle, anagen induction, hair cycle, adenoviral gene transfer, Patched receptor, Gli1, melanogenesis, tyrosinase, epithelial invagination, hair follicle development
- MeSH terms
- Adenoviridae, Aging, Animals, Epithelial Cells, Genetic Vectors, Hair, Mice, Inbred C57BL, Mice, Transgenic, Proteins, Skin, Trans-Activators, Sequence Deletion, Mice, Knockout, Gene Expression Regulation, Developmental, Hair Follicle, Mice, Hedgehog Proteins
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