Noggin is a mesenchymally derived stimulator of hair-follicle induction

Vladimir A. Botchkarev, Natalia V. Botchkareva, Wera Roth, Motonobu Nakamura, Ling Hong Chen, Wiebke Herzog, Gerd Lindner, Jill A. McMahon, Christoph Peters, Roland Lauster, Andrew P. McMahon, Ralf Paus

Research output: Contribution to journalArticlepeer-review

304 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalNature Cell Biology
Volume1
Issue number3
DOIs
StatePublished - Jul 1999
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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