Conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration

Citation
Lc. Wang et al., Conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration, J INVES DER, 114(5), 2000, pp. 901-908
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022-202X → ACNP
Volume
114
Issue
5
Year of publication
2000
Pages
901 - 908
Database
ISI
SICI code
0022-202X(200005)114:5<901:CDOHSP>2.0.ZU;2-Q
Abstract
Members of the vertebrate hedgehog family (Sonic, Indian, and Desert) have been shown to be essential for the development of various organ systems, in cluding neural, somite, limb, skeletal, and for male gonad morphogenesis. S onic hedgehog and its cognate receptor Patched are expressed in the epithel ial and/or mesenchymal cell components of the hair follicle. Recent studies have demonstrated an essential role for this pathway in hair development i n the skin of Sonic hedgehog null embryos. We have further explored the rol e of the hedgehog pathway using anti-hedgehog blocking monoclonal antibodie s to treat pregnant mice at different stages of gestation and have generate d viable offspring that lack body coat hair. Histologic analysis revealed t he presence of ectodermal placode and primodium of dermal papilla in these mice, yet the subsequent hair shaft formation was inhibited. In contrast, t he vibrissae (whisker) development appears to be unaffected upon anti-hedge hog blocking monoclonal antibody treatment. Strikingly, inhibition of body coat hair morphogenesis also was observed in mice treated postnatally with anti-hedgehog monoclonal antibody during the growing (anagen) phase of the hair cycle. The hairless phenotype was reversible upon suspension of monocl onal antibody treatment. Taken together, our results underscore a direct ro le of the Sonic hedgehog signaling pathway in embryonic hair follicle devel opment as well as in subsequent hair cycles in young and adult mice. Our sy stem of generating an inducible and reversible hairless phenotype by anti-h edgehog monoclonal antibody treatment will be valuable for studying the reg ulation and mechanism of hair regeneration.