title: Noggin is a mesenchymally derived stimulator of hair-follicle induction.
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.
authors.affiliation: Department of Dermatology, Charité, Humboldt-University Berlin, Germany.
authors.forename: V A
authors.initials: VA
authors.lastname: Botchkarev
authors.forename: N V
authors.initials: NV
authors.lastname: Botchkareva
authors.forename: W
authors.initials: W
authors.lastname: Roth
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: L H
authors.initials: LH
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Herzog
authors.forename: G
authors.initials: G
authors.lastname: Lindner
authors.forename: J A
authors.initials: JA
authors.lastname: McMahon
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: R
authors.initials: R
authors.lastname: Lauster
authors.forename: A P
authors.initials: AP
authors.lastname: McMahon
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000196:embryology*; D006579:Heterozygote; D007633:Keratins / Q000235:genetics; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009924:Organ Culture Techniques; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics; D017978:Receptors, Growth Factor; D012867:Skin / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D007633:Keratins; D011506:Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse