Laminin-10 is crucial for hair morphogenesis.
The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (alpha5beta1gamma1) in hair follicle development. Laminin-10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin-10 in hair development. Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia. E16.5 Lama5 -/- mouse skin, lacking laminin-10, contained fewer hair germs compared with controls, and after transplantation, Lama5 -/- skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 -/- skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 -/- skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin-10 in developmental signaling. Intriguingly, treatment of Lama5 -/- skin with purified laminin-10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin-10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.
Program in Epithelial Biology, Stanford University School of Medicine, 269 Campus Drive, Room 2145, CA 94305, USA.
Jie
J
Li
Julia
J
Tzu
Yi
Y
Chen
Yan-Ping
YP
Zhang
Ngon T
NT
Nguyen
Jing
J
Gao
Maria
M
Bradley
Douglas R
DR
Keene
Anthony E
AE
Oro
Jeffrey H
JH
Miner
M Peter
MP
Marinkovich
D000505:Alopecia / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006197:Hair / Q000196:embryology* / Q000254:growth & development; D018859:Hair Follicle / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D017403:In Situ Hybridization; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009024:Morphogenesis; D014183:Transplantation, Heterologous
D016023:Integrins; D007797:Laminin; C119013:laminin 10