title: Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.
abstract: Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China. yangling24@hotmail.com.|Department of Cell and Molecular Biology, Tulane University, New Orleans, LA7 0118, USA. yangling24@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA7 0118, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA7 0118, USA.
authors.forename: Wenduo
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA7 0118, USA.|Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Science, Fujian Normal University, Fuzhou, Fujian, 350108, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA7 0118, USA. ychen@tulane.edu.|Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Science, Fujian Normal University, Fuzhou, Fujian, 350108, China. ychen@tulane.edu.
authors.forename: YiPing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D019465:Craniofacial Abnormalities / Q000196:embryology* / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000196:embryology* / Q000473:pathology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013705:Temporomandibular Joint Disorders / Q000196:embryology* / Q000235:genetics / Q000473:pathology
chemical_list: D053823:Hedgehog Proteins; C514061:ihh protein, mouse
keywords: Condyle; Cranial neural crest; Glenoid fossa; Indian hedgehog; Temporomandibular joint