Botchkarev V A, Botchkareva N V, Roth W, Nakamura M, Chen L H, Herzog W, Lindner G, McMahon J A, Peters C, Lauster R, McMahon A P, Paus R
Department of Dermatology, Charité, Humboldt-University Berlin, Germany.
Nat Cell Biol. 1999 Jul;1(3):158-64. doi: 10.1038/11078.
The induction of developmental structures derived from the ectoderm, such as 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 neural inducer and BMP-neutralizing protein Noggin is expressed in the follicular mesenchyme, that noggin-knockout mice show significant retardation of hair-follicle induction, and that Noggin neutralizes the inhibitory action of BMP-4 and stimulates hair-follicle induction in embryonic skin organ culture. 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 molecule NCAM, as well as through BMP4-independent downregulation of the 75 kD neurotrophin receptor in the developing hair follicle.
外胚层衍生的发育结构，如神经管或牙齿的诱导，是通过骨形态发生蛋白（BMP）家族成员的抑制活性被BMP拮抗剂中和来实现的。在这里，我们表明，在毛囊发育过程中，神经诱导剂和BMP中和蛋白Noggin在毛囊间充质中表达，Noggin基因敲除小鼠的毛囊诱导明显延迟，并且Noggin在胚胎皮肤器官培养中中和BMP-4的抑制作用并刺激毛囊诱导。作为刺激毛囊诱导的关键间充质信号，Noggin通过与BMP-4的拮抗相互作用发挥作用，这导致转录因子Lef-1和细胞粘附分子NCAM的上调，以及通过不依赖BMP4的方式下调发育中的毛囊中的75 kD神经营养因子受体。
