020 Analysis of hair development in follistatin-deficient mice and BMP-7 knockout mice

M Nakamura1, K Foitzik1, S Liotiri1, M Matzuk2, R Godin3, E J Robertson3, and R Paus1 1Dept. of Dermatology, University Hospital Eppendorf, Hamburg, Germany 2Dept. of Pathology and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA 3Dept. of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA

Follistatin usually antagonizes the action of activin, BMP-2, BMP-4, and BMP-7 by binding them. Expression of BMP-7 has been reported in the inner root and outer root sheath as well as in the follicular dermal papilla. Since follistatin-deficient mice show abnormalities in vibrissae follicle development, we have further explored the role of follistatin and one of its signalling partners, BMP-7, in murine hair follicle development. In situ hybridization revealed that follistatin is expressed in the outer and inner root sheath, all layers of the interfollicular epidermis and most strongly in hair matrix cells. Compared to wild type controls, follistatin knockout mice showed a significant retardation of hair follicle morphogenesis (p < 0.01). The follistatin null mutation also significantly reduced keratinocyte proliferation in stage 1-2 hair follicles. However, BMP-7-deficient mice showed no significant abnormalities in hair follicle morphogenesis, keratinocyte proliferation, hair follicle density, or epidermal thickness. Immunohistological analysis of apoptotic cells (TUNEL), selected adhesion molecules (NCAM), morphogens (KGF), or growth factor receptors (FGFR-2, m-met) failed to reveal any substantial changes in both knockout strains, compared to wildtype controls. In organ culture of human anagen VI scalp hair follicles, recombinant human follistatin inhibited hair shaft elongation and induced premature hair follicle regression (catagen). Taken together, these data suggest that follistatin is involved in the control of both hair follicle morphogenesis and hair cycling, while BMP-7 does not play an indispensable role in hair and skin biology.