L5.      BMP signalling regulates size of the hair follicles via modulating the expression of cell cycle-associated genes.
Andrey Sharov, Tatyana Sharova, Ruzanna Atoyan, Andrei Mardariev, Vladimir Botchkarev; Department of Dermatology, Boston University School of Medicine, USA.

Bone morphogenetic protein (BMP) signaling is involved in regulation of a large variety of developmental programs including those controlling the organ size. Here, we show that transgenic mice overexpressing BMP antagonist noggin (promoter: K5) are characterized by marked increase of size of the anagen hair follicles (HFs) and by replacement of zig-zag hairs by awl-like hairs, compared to the age-matched wild-type controls. In K5-Noggin mice, increase in size of the hair bulb is not accompanied by any significant changes in size or cellularity of the follicular papilla. However, markedly enlarged anagen HFs of K5-Noggin mice show increased proliferation in the matrix and increased number of the hair cortex and medulla cells, compared to wild-type HFs. Microarray and real-time PCR analyses of the laser captured hair matrix cells show strong decrease in expression of cyclin-dependent kinase inhibitor p27Kip1 and increased expression of selected cyclins in K5-Noggin versus wild-type mice. Similarly to K5-Noggin mice, p27Kip1 knockout mice also show increased size of anagen HFs associated with increased cell proliferation in the hair bulb. Activation of BMP signaling in HaCaT keratinocytes induces growth arrest, stimulates p27Kip1 expression and positively regulates p27Kip1 promoter activity, thus further supporting a role of p27Kip1 in mediating the effects of BMP signaling on HF size. These data suggest that BMP signaling plays important role in regulating cell proliferation and controls size of anagen HFs via follicular papilla-independent modulation of the expression of cell-cycle associated genes in hair matrix keratinocytes.