Sulfotransferase Ndst1 is Needed for Mandibular and TMJ Development

• Published in: Journal of dental research Vol. 89; no. 10; pp. 1111 - 1116
• Main Authors: Yasuda, T., Mundy, C., Kinumatsu, T., Shibukawa, Y., Shibutani, T., Grobe, K., Minugh-Purvis, N., Pacifici, M., Koyama, E.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-10-2010; International Association for Dental Research; SAGE PUBLICATIONS, INC
• Subjects: Animals; Apoptosis; Biological and medical sciences; Chondrocytes - pathology; Dentistry; Development. Metamorphosis. Moult. Ageing; Diseases of the osteoarticular system; Endothelium, Vascular - abnormalities; Endothelium, Vascular - embryology; Facial Asymmetry - embryology; Facial Asymmetry - pathology; Fundamental and applied biological sciences. Psychology; Golgi Apparatus - enzymology; Growth Plate - abnormalities; Growth Plate - embryology; Hedgehog Proteins - physiology; Heparan Sulfate Proteoglycans - physiology; Imaging, Three-Dimensional; Incisor - abnormalities; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Mandible - abnormalities; Mandible - embryology; Mandible - enzymology; Mandibular Condyle - abnormalities; Mandibular Condyle - embryology; Maxilla - abnormalities; Maxilla - embryology; Medical sciences; Mice; Mice, Mutant Strains; Molar - abnormalities; Ossification, Heterotopic - embryology; Ossification, Heterotopic - pathology; Penetrance; Research Reports; Sulfotransferases - physiology; Temporomandibular Joint - abnormalities; Temporomandibular Joint - embryology; Temporomandibular Joint - enzymology; Tooth Germ - abnormalities; Vertebrates: anatomy and physiology, studies on body, several organs or systems; X-Ray Microtomography; Ndst1; TMJ; heparan sulfate; hemifacial microsomia; hedgehog signaling; Proteoglycan; Sulfotransferases; Embryo; Diseases of the osteoarticular system; Temporomandibular joint; Osteoarticular system; Signal transduction; Development; Heparitin sulfate; Face; Mandible; Enzyme; Transferases; Rodentia; Dysostosis; Vertebrata; Mammalia; Mouse; Malformation; Animal; Hemifacial microsomia
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034510373766

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.