Noggin is a mesenchymally derived stimulator of hair-follicle induction

The induction of developmental structures derived from the ectoderm, such a s the neural tube or tooth, occurs through neutralization of the inhibitory activity of members of the bone-morphogenetic protein (BMP) family by BMP antagonists. Here we show that, during hair-follicle development, the neura l inducer and BMP-neutralizing protein Noggin is expressed in the follicula r mesenchyme, that noggin-knockout mice show significant retardation of hai r-follicle induction, and that Noggin neutralizes the inhibitory action of BMP-4 and stimulates hair-follicle induction in embryonic skin organ cultur e. As a crucial mesenchymal signal that stimulates hair-follicle induction, Noggin operates through antagonistic interactions with BMP-4, which result in upregulation of the transcription factor Lef-1 and the cell-adhesion mo lecule NCAM, as well as through BMP4-independent downregulation of the 75 k D neurotrophin receptor in the developing hair follicle.