Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

22 (10): 2400-2410

Copyright © 2003 by the European Molecular Biology Organization.

Laminin-10 is crucial for hair morphogenesis

Jie Li1,2, Julia Tzu1, Yi Chen1, Yan-Ping Zhang3, Ngon T. Nguyen1, Jing Gao1, Maria Bradley1, Douglas R. Keene4, Anthony E. Oro1, Jeffrey H. Miner5, and M.Peter Marinkovich1,6,7

1 Program in Epithelial Biology, Stanford University School of Medicine, 269 Campus Drive, Room 2145, Stanford, CA 94305, 3 Department of Dermatology, University of Miami School of Medicine, Miami, FL 33136, 4 Imaging Center, Shriners Hospital for Children, Portland, OR 97201, 5 Renal Division and Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110 and 6 Dermatology Service, Palo Alto VA Health Care System, Palo Alto, CA 94304, USA 2 Present address: Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, FL 33136, USA 7 Corresponding author e-mail: mpm{at}stanford.edu

Abstract: The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 ({alpha}5ß1{gamma}1) 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 ß1 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.

Key Words: Keywords: basement membrane/extracellular matrix/hair follicle/laminin



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882