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  • The EMBO Journal (2003) 22, 2400 - 2410
  • doi:10.1093/emboj/cdg239

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

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

Correspondence to:

M. Peter Marinkovich, E-mail: mpm@stanford.edu

Received 23 October 2002; Accepted 24 March 2003

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.

  • Keywords:

    • basement membrane,
    • extracellular matrix,
    • hair follicle,
    • laminin