Laminin-10 is crucial for hair morphogenesis

Jie Li, Julia Tzu, Yi Chen, Yan Ping Zhang, Ngon T. Nguyen, Jing Gao, Maria Bradley, Douglas R. Keene, Anthony E. Oro, Jeffrey H. Miner, M. Peter Marinkovich

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2400-2410
Number of pages11
JournalEMBO Journal
Volume22
Issue number10
DOIs
StatePublished - May 15 2003

Keywords

  • Basement membrane
  • Extracellular matrix
  • Hair follicle
  • Laminin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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