Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog
Noboru Sato, … , Philip L. Leopold, Ronald G. Crystal
Noboru Sato, … , Philip L. Leopold, Ronald G. Crystal
Published October 1, 1999
Citation Information: J Clin Invest. 1999;104(7):855-864. https://doi.org/10.1172/JCI7691.
View: Text | PDF
Article Article has an altmetric score of 9

Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog

Abstract

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.

Authors

Noboru Sato, Philip L. Leopold, Ronald G. Crystal

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Localization of Shh expression in skin by in situ hybridization before a...
Localization of Shh expression in skin by in situ hybridization before and after administration of AdShh. Paraffin sections of mouse skin during its natural anagen period (postnatal day 33) compared with postnatal day 22 naive mouse skin or skin of mice injected on postnatal day 19 with PBS, AdNull, or AdShh. The sections were analyzed by in situ hybridization using [33P]UTP-labeled antisense and sense Shh riboprobes. After hybridization, sites of probe binding were identified using a photographic emulsion, and tissue was stained with hematoxylin and eosin. Arrows indicate positive staining for Shh mRNA. Closed arrowheads indicate melanosomes in the hair follicle. Open arrowheads indicate melanin in hair shafts. (a) Anagen skin from a naive 33-day-old mouse (positive control) hybridized with an antisense Shh complementary to Shh mRNA. (b) Adjacent tissue section of anagen skin hybridized with a sense Shh probe. (c) Naive postnatal day 22 skin hybridized with an antisense Shh probe. (d) Postnatal day 22 skin 3 days after injection with 108 PFU of AdNull hybridized with an antisense Shh probe. (e) Postnatal day 22 skin 3 days after injection of 108 PFU of AdShh hybridized with an antisense Shh probe. (f) Postnatal day 22 skin 3 days after injection with 108 PFU of AdShh hybridized with a sense Shh probe. (g–i) High-magnification examples of cells in AdShh-injected mouse skin hybridized with antisense Shh probe. Scale bar: 50 μm.