title: Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression.
abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient's hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin expression.
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, Jinan Wen Hua Xi Road 44, Jinan 250012, PR China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Sato
authors.affiliation: First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Oikawa
authors.affiliation: First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan. Electronic address: ymuragak@wakayama-med.ac.jp.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Muragaki
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, Jinan Wen Hua Xi Road 44, Jinan 250012, PR China. Electronic address: zhougy@sdu.edu.cn.
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D049109:Cell Proliferation; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D050980:GATA Transcription Factors / Q000235:genetics / Q000502:physiology*; D006201:Hair Diseases / Q000235:genetics*; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D006801:Humans; D015826:Langer-Giedion Syndrome / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009666:Nose / Q000002:abnormalities*; D012097:Repressor Proteins; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D050980:GATA Transcription Factors; D012097:Repressor Proteins; D000099176:Noggin Protein; C525953:Trps1 protein, mouse
keywords: BMP; Development; Hair follicle; Noggin; Trps1