TY - JOUR
T1 - Laminin-10 is crucial for hair morphogenesis
AU - Li, Jie
AU - Tzu, Julia
AU - Chen, Yi
AU - Zhang, Yan Ping
AU - Nguyen, Ngon T.
AU - Gao, Jing
AU - Bradley, Maria
AU - Keene, Douglas R.
AU - Oro, Anthony E.
AU - Miner, Jeffrey H.
AU - Marinkovich, M. Peter
PY - 2003/5/15
Y1 - 2003/5/15
N2 - The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (α5β1γ1) 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 β1 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.
AB - The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (α5β1γ1) 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 β1 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.
KW - Basement membrane
KW - Extracellular matrix
KW - Hair follicle
KW - Laminin
UR - http://www.scopus.com/inward/record.url?scp=0038242298&partnerID=8YFLogxK
U2 - 10.1093/emboj/cdg239
DO - 10.1093/emboj/cdg239
M3 - Article
C2 - 12743034
AN - SCOPUS:0038242298
SN - 0261-4189
VL - 22
SP - 2400
EP - 2410
JO - EMBO Journal
JF - EMBO Journal
IS - 10
ER -