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.
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Article

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

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Figure 4

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Hair growth in C57BL/6 mice after intradermal administration of AdShh du...
Hair growth in C57BL/6 mice after intradermal administration of AdShh during first telogen. AdShh, AdNull, or PBS was administered to the dorsal skin of postnatal day 19 C57BL/6 mice. Five days after administration, dorsal hair was bleached with blonde hair dye to provide contrast for assessing new growth of the natural black hair of the mice. On day 7, the dorsal hair was clipped. (a and b) Mice at day 7 after administration of AdShh. Shown are 2 example pairs. The injection site in AdNull-treated animals was indistinct (left-side mice), whereas melanogenesis was evident at the site of AdShh injection in AdShh-treated mice (right-side mice). (c and d) Mice at day 14 after administration of AdShh. Shown are 2 example pairs. The injection site in AdNull-treated animals was indistinct (left-side mice). New hair growth is seen (note black color relative to preexisting dyed hair) at the site of AdShh injection (right-side mice). (e) Lateral aspect of day 14 AdShh-treated mouse showing length of hair growth at injection site. (f) High magnification of injection site showing new black hair and preexisting blonde-dyed hair. Scale bar: 2 mm. (g) Scanning electron microscopic analysis of normal C57BL/6 mouse hair shaft. (h) Scanning electron microscopic analysis of C57BL/6 mouse hair shaft induced by intradermal injection of AdShh (day 14 after vector administration). Scale bar: 10 μm. (i) Spatial distribution of transgene expression. Adβgal (108 PFU), an E1–E3– Ad vector expressing the Escherichia coli βgal marker gene, was injected intradermally on the dorsal surface of postnatal day 19 C57BL/6 mice. On day 0 and on day 2, a single strip of dorsal skin along the cephalocaudal axis was harvested, divided into 5 equal 2.5-mm segments (see diagram below graph; 0 = site of infection), and assayed for βgal activity (data from 3 animals are shown). The gray area corresponds to the size and position of the wheal (7–10 mm in diameter) formed at the site of injection. Data are expressed as βgal activity per mg protein. The anatomic distribution of the marker gene is similar to that of the melanogenesis and new hair growth observed in b and c.