title: Ihh signaling regulates mandibular symphysis development and growth.
abstract: Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.
authors.affiliation: Department of Surgery, The Children's Hospital of Philadelphia Research Institute, 3615 Civic Center Boulevard, Abramson Research Center, 902 Philadelphia, PA 19104, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sugito
authors.forename: Y
authors.initials: Y
authors.lastname: Shibukawa
authors.forename: T
authors.initials: T
authors.lastname: Kinumatsu
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Nagayama
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Minugh-Purvis
authors.forename: M
authors.initials: M
authors.lastname: Pacifici
authors.forename: E
authors.initials: E
authors.lastname: Koyama
mesh_terms: D000818:Animals; D002356:Cartilage / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D049109:Cell Proliferation; D002680:Chin / Q000196:embryology / Q000254:growth & development*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics*; D024121:Collagen Type X / Q000096:biosynthesis; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000196:embryology; D053823:Hedgehog Proteins / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000502:physiology; D008334:Mandible / Q000196:embryology / Q000254:growth & development*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000502:physiology; D053495:Osteopontin / Q000096:biosynthesis; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D000074290:Zinc Finger Protein Gli3
chemical_list: D024121:Collagen Type X; D053823:Hedgehog Proteins; D006497:Heparan Sulfate; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D053495:Osteopontin; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D000074290:Zinc Finger Protein Gli3; C465571:Gli3 protein, mouse; C000606240:Ptch1 protein, mouse; C514061:ihh protein, mouse