Abstract
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.
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Acknowledgements
We thank R. Pliet for technical assistance; R. Harland for providing the Noggin-producing cell line; A. Vortkamp and E. Chelkovnikova for the purification of Noggin protein; and O. Huber and K. Funa for supplying plasmids and antisera. This study was supported by a grant from the Deutsche Forschungsgemeinschaft to R.P. (Pa 345/8-2). Work in A.P.M.’s laboratory is supported by grants from the NIH.
Correspondence and requests for materials should be addressed to R.P. or V.A.B.
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Botchkarev, V., Botchkareva, N., Roth, W. et al. Noggin is a mesenchymally derived stimulator of hair-follicle induction . Nat Cell Biol 1, 158–164 (1999). https://doi.org/10.1038/11078
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DOI: https://doi.org/10.1038/11078
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