Laminin-10 is crucial for hair morphogenesis

EMBO J. 2003 May 15;22(10):2400-10. doi: 10.1093/emboj/cdg239.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alopecia / metabolism
  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / ultrastructure
  • Cells, Cultured
  • Embryo, Mammalian / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelium / metabolism
  • Hair / embryology*
  • Hair / growth & development
  • Hair Follicle / embryology*
  • Hair Follicle / growth & development
  • Humans
  • In Situ Hybridization
  • Integrins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Laminin / genetics
  • Laminin / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • Morphogenesis*
  • Transplantation, Heterologous

Substances

  • Integrins
  • Laminin
  • laminin 10