Hair follicles are required for hair growth and also provide a reservoir of stem cells that are believed to play a role in wound healing; abnormal follicle development can lead to neoplastic conditions such as basal cell carcinoma. Hair follicle development involves interactions between mesenchyme and epithelium in which various secreted proteins including sonic hedgehog (Shh), which is critical for hair follicle development, play some role. Extracellular matrix molecules in the basement membrane zone (BMZ) at the epithelial-mesenchymal interface have also been implicated in follicle development. The exact role of the BMZ, however, is poorly understood. Li et al. used indirect immunofluorescence microscopy to identify laminin-10 as the predominant laminin in the BMZ underlying elongating hair follicles in embryonic mouse skin. Injection of antibodies to human laminin-10 into nude mice bearing human scalp xenografts led to alopecia and a lack of follicles in the graft. Skin from embryonic mutant mice that lack laminin-10 had reduced numbers of hair germs. Grafts from the mutant mice (which do not survive beyond embryonic day 16.5) showed evidence of further follicular regression over time. The mutant grafts showed defects in the basement membrane, decreased follicular cell proliferation, and decreased expression of Shh and its target Gli1. Incubating the mutant skin in human laminin-10 before grafting restored hair follicle development. These data establish a role for the BMZ protein laminin-10 in follicular morphogenesis and represent the first example of an exogenous protein being used to rectify a cutaneous developmental problem.
J. Li, J. Tzu, Y. Chen, Y.-P. Zhang, N. T. Nguyen, J. Gao, M. Bradley, D. R. Keene, A. E. Oro, J. H. Miner, M. P. Marinkovich, Laminin-10 is crucial for hair morphogenesis. EMBO J. 22, 2400-2410 (2003). [Abstract] [Full Text]