Modulation of BMP signaling by noggin is required for induction of the secondary (nontylotrich) hair follicles.
Increasing evidence suggests that morphogenesis of the distinct developmental structures derived from the same organ-committed epithelium is controlled by differential mechanisms. As was recently shown in mice with mutations in the downless (dL) gene, induction of primary or tylotrich hair follicles is strikingly dependent of signaling through the Tnf receptor homologue, Edar. Here, we show that dorsal skin of murine embryos with constitutive deletion of the BMP2/4 antagonist noggin, after transplantation into SCID mice, is characterized by the lack of induction of secondary hair follicles, and by the arrest of primary hair follicle development prior to hair shaft formation. The loss of noggin activity was associated with failure to express genes that specify hair follicle cell fates in the epidermis (Lef-1, beta-catenin, Shh) and dermal papilla (p75 kDa neurotrophin receptor, alkaline phosphatase). This suggests that regulation of BMP2/4 signaling by noggin is essential for the induction of secondary hair follicles, as well as for advanced stages of development in primary hair follicles.
Botchkarev
Vladimir A
VA
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. vladbotc@bu.edu
Botchkareva
Natalia V
NV
Sharov
Andrei A
AA
Funa
Keiko
K
Huber
Otmar
O
Gilchrest
Barbara A
BA
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002352:Carrier Proteins; D020405:Dermis / Q000196:embryology; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D004817:Epidermis / Q000196:embryology; D016332:Fetal Tissue Transplantation; D018859:Hair Follicle / Q000002:abnormalities / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology / Q000235:genetics; D016513:Mice, SCID; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000196:embryology; D016038:Skin Transplantation; D016212:Transforming Growth Factor beta; D015854:Up-Regulation; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse