title: Sulfotransferase Ndst1 is needed for mandibular and TMJ development.
abstract: Heparan sulfate proteoglycans (HS-PGs) regulate several developmental processes, but their possible roles in mandibular and TMJ formation are largely unclear. To uncover such roles, we generated mice lacking Golgi-associated N-sulfotransferase 1 (Ndst1) that catalyzes sulfation of HS-PG glycosaminoglycan chains. Ndst1-null mouse embryos exhibited different degrees of phenotypic penetrance. Severely affected mutants lacked the temporomandibular joint and condyle, but had a mandibular remnant that displayed abnormal tooth germs, substandard angiogenesis, and enhanced apoptosis. In mildly affected mutants, the condylar growth plate was dysfunctional and exhibited thicker superficial and polymorphic cell zones, a much wider distribution of Indian hedgehog signaling activity, and ectopic ossification along its lateral border. Interestingly, mildly affected mutants also exhibited facial asymmetry resembling that seen in individuals with hemifacial microsomia. Our findings indicate that Ndst1-dependent HS sulfation is critical for mandibular and TMJ development and allows HS-PGs to exert their roles via regulation of Ihh signaling topography and action.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, 1015 Walnut Street, Curtis Building Room 501, Philadelphia, PA 19107, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: C
authors.initials: C
authors.lastname: Mundy
authors.forename: T
authors.initials: T
authors.lastname: Kinumatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Shibukawa
authors.forename: T
authors.initials: T
authors.lastname: Shibutani
authors.forename: K
authors.initials: K
authors.lastname: Grobe
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; D017209:Apoptosis; D019902:Chondrocytes / Q000473:pathology; D004730:Endothelium, Vascular / Q000002:abnormalities / Q000196:embryology; D005146:Facial Asymmetry / Q000196:embryology / Q000473:pathology; D006056:Golgi Apparatus / Q000201:enzymology; D006132:Growth Plate / Q000002:abnormalities / Q000196:embryology; D053823:Hedgehog Proteins / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D021621:Imaging, Three-Dimensional; D007180:Incisor / Q000002:abnormalities; D008334:Mandible / Q000002:abnormalities / Q000196:embryology* / Q000201:enzymology; D008335:Mandibular Condyle / Q000002:abnormalities / Q000196:embryology; D008437:Maxilla / Q000002:abnormalities / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D008963:Molar / Q000002:abnormalities; D009999:Ossification, Heterotopic / Q000196:embryology / Q000473:pathology; D019683:Penetrance; D015238:Sulfotransferases / Q000502:physiology*; D013704:Temporomandibular Joint / Q000002:abnormalities / Q000196:embryology* / Q000201:enzymology; D014083:Tooth Germ / Q000002:abnormalities; D055114:X-Ray Microtomography
chemical_list: D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; C514061:ihh protein, mouse; D015238:Sulfotransferases; C021350:heparitin sulfotransferase