Spry1 and spry2 are essential for development of the temporomandibular joint.
The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw. The main components of the TMJ are the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between them. The genetic program for the development of the TMJ remains poorly understood. Here we show the crucial role of sprouty (Spry) genes in TMJ development. Sprouty genes encode intracellular inhibitors of receptor tyrosine kinase (RTK) signaling pathways, including those triggered by fibroblast growth factors (Fgfs). Using in situ hybridization, we show that Spry1 and Spry2 are highly expressed in muscles attached to the TMJ, including the lateral pterygoid and temporalis muscles. The combined inactivation of Spry1 and Spry2 results in overgrowth of these muscles, which disrupts normal development of the glenoid fossa. Remarkably, condyle and disc formation are not affected in these mutants, demonstrating that the glenoid fossa is not required for development of these structures. Our findings demonstrate the importance of regulated RTK signaling during TMJ development and suggest multiple skeletal origins for the fossa. Notably, our work provides the evidence that the TMJ condyle and disc develop independently of the mandibular fossa.
Department of Plastic and Oral Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. patricia.purcell@childrens.harvard.edu
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Purcell
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Jheon
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Vivero
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Rahimi
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Joo
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Klein
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000963:Antimetabolites; D017209:Apoptosis / Q000235:genetics; D001973:Bromodeoxyuridine; D053148:Caspase 3 / Q000032:analysis; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D020868:Gene Silencing; D005865:Gestational Age; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008335:Mandibular Condyle / Q000196:embryology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011626:Pterygoid Muscles / Q000196:embryology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013701:Temporal Bone / Q000196:embryology; D013703:Temporal Muscle / Q000196:embryology; D013704:Temporomandibular Joint / Q000196:embryology*; D019224:Temporomandibular Joint Disc / Q000196:embryology; D055114:X-Ray Microtomography
D048868:Adaptor Proteins, Signal Transducing; D000963:Antimetabolites; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D001973:Bromodeoxyuridine