039 Noggin is required for induction and cyclic activity of the secondary (non-tylotrich) hair follicles

V. A. Botchkarev1, N. V. Botchkareva1, M. Nakamura2, O. Huber3, K. Funa4, R. Lauster5, R.Paus2 and B. A. Gilchrest1. 1Dept. of Dermatology, Boston University School of Medicine, Boston, USA; 2Dept. of Dermatology, University of Hamburg, Hamburg, Germany; 3Free University Berlin, Germany; 4University of Geteborg, Sweden; 5Deutsche Rheumaforschunzentrum, Berlin, Germany

Increased evidence of data suggests that morphogenesis of the hair follicle (HF) and its cyclic activation during postnatal development are both regulated by similar mechanisms. Here, we show that embryonic skin of mice with constitutive deletion of the bone morphogenetic protein (BMP) antagonist noggin, after transplantation into SCID mice, is characterized by the lack of induction of secondary HF, which make up 90-95% in mouse fur. The loss of noggin activity is associated with failure to express genes that specify HF cell fates in skin (Lef-1, beta-catenin, Shh, p75NTR). By semi-quantitative RT-PCR, in situ hybridization, and immunohistology of C57BL/6 murine postnatal skin, BMP4 and BMPR-IA are prominently expressed in the resting (telogen) HF, while hair growth phase (anagen) initiation is associated with upregulation of noggin message. Furthermore, BMP4 causes selective arrest of the telogen-anagen transition and anagen development in the secondary HF, while noggin induces new anagen in the telogen skin. As a hair growth inducer, noggin increases Shh in the HF, while BMP4 downregulates Shh. This suggests that molecular mechanisms, driving induction and anagen initiation in the secondary HF, are more highly conserved than previously appreciated and both require modulation of BMP signaling by noggin.