title: Abnormal hair development and apparent follicular transformation to mammary gland in the absence of hedgehog signaling.
abstract: We show that removing the Shh signal tranducer Smoothened from skin epithelium secondarily results in excess Shh levels in the mesenchyme. Moreover, the phenotypes we observe reflect decreased epithelial Shh signaling, yet increased mesenchymal Shh signaling. For example, the latter contributes to exuberant hair follicle (HF) induction, while the former depletes the resulting follicular stem cell niches. This disruption of the niche apparently also allows the remaining stem cells to initiate hair formation at inappropriate times. Thus, the temporal structure of the hair cycle may depend on the physical structure of the niche. Finally, we find that the ablation of epithelial Shh signaling results in unexpected transformations: the follicular outer root sheath takes on an epidermal character, and certain HFs disappear altogether, having adopted a strikingly mammary gland-like fate. Overall, our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.
authors.affiliation: Department of Oral Biochemistry, Sahlgrenska Academy at Göteborg University, Medicinaregatan 12F, Göteborg, Sweden. amel@odontologi.gu.se
authors.forename: Amel
authors.initials: A
authors.lastname: Gritli-Linde
authors.forename: Kristina
authors.initials: K
authors.lastname: Hallberg
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Azadeh
authors.initials: A
authors.lastname: Reyahi
authors.forename: Marie
authors.initials: M
authors.lastname: Kannius-Janson
authors.forename: Jeanette
authors.initials: J
authors.lastname: Nilsson
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Cobourne
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.forename: Anders
authors.initials: A
authors.lastname: Linde
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D004475:Ectoderm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D019426:Integrases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology*; D008648:Mesoderm / Q000166:cytology; D008679:Metaplasia; D051379:Mice; D009024:Morphogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013234:Stem Cells / Q000166:cytology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases