title: Regular articles: conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration.
abstract: Members of the vertebrate hedgehog family (Sonic, Indian, and Desert) have been shown to be essential for the development of various organ systems, including neural, somite, limb, skeletal, and for male gonad morphogenesis. Sonic hedgehog and its cognate receptor Patched are expressed in the epithelial and/or mesenchymal cell components of the hair follicle. Recent studies have demonstrated an essential role for this pathway in hair development in the skin of Sonic hedgehog null embryos. We have further explored the role of the hedgehog pathway using anti-hedgehog blocking monoclonal antibodies to treat pregnant mice at different stages of gestation and have generated viable offspring that lack body coat hair. Histologic analysis revealed the presence of ectodermal placode and primodium of dermal papilla in these mice, yet the subsequent hair shaft formation was inhibited. In contrast, the vibrissae (whisker) development appears to be unaffected upon anti-hedgehog 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 monoclonal antibody treatment. Taken together, our results underscore a direct role of the Sonic hedgehog signaling pathway in embryonic hair follicle development as well as in subsequent hair cycles in young and adult mice. Our system of generating an inducible and reversible hairless phenotype by anti-hedgehog monoclonal antibody treatment will be valuable for studying the regulation and mechanism of hair regeneration.
authors.affiliation: Biogen Inc, Cambridge, Massachusetts 02142, USA. lichun_wang@biogen.com
authors.forename: L C
authors.initials: LC
authors.lastname: Wang
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Gambardella
authors.forename: A
authors.initials: A
authors.lastname: Delacour
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: I
authors.initials: I
authors.lastname: Sizing
authors.forename: P
authors.initials: P
authors.lastname: Rayhorn
authors.forename: E A
authors.initials: EA
authors.lastname: Garber
authors.forename: C D
authors.initials: CD
authors.lastname: Benjamin
authors.forename: K P
authors.initials: KP
authors.lastname: Williams
authors.forename: F R
authors.initials: FR
authors.lastname: Taylor
authors.forename: Y
authors.initials: Y
authors.lastname: Barrandon
authors.forename: L
authors.initials: L
authors.lastname: Ling
authors.forename: L C
authors.initials: LC
authors.lastname: Burkly
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D029721:Drosophila Proteins; D005260:Female; D006197:Hair / Q000196:embryology* / Q000502:physiology; D053823:Hedgehog Proteins; D006801:Humans; D019476:Insect Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D011247:Pregnancy; D012038:Regeneration
chemical_list: D000911:Antibodies, Monoclonal; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; C077245:hh protein, Drosophila