Noggin is a mesenchymally derived stimulator of hair-follicle induction.
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.
Botchkarev
V A
VA
Department of Dermatology, Charité, Humboldt-University Berlin, Germany.
Botchkareva
N V
NV
Roth
W
W
Nakamura
M
M
Chen
L H
LH
Herzog
W
W
Lindner
G
G
McMahon
J A
JA
Peters
C
C
Lauster
R
R
McMahon
A P
AP
Paus
R
R
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
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