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PMID:17191253

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Citation

Shibukawa, Y, Young, B, Wu, C, Yamada, S, Long, F, Pacifici, M and Koyama, E (2007) Temporomandibular joint formation and condyle growth require Indian hedgehog signaling. Dev. Dyn. 236:426-34

Abstract

The temporomandibular joint (TMJ) is essential for jaw function, but the mechanisms regulating its development remain poorly understood. Because Indian hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible roles in TMJ development. In wild-type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia. In Ihh(-/-) embryos, TMJ development was severely compromised. Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal. These severe defects were partially corrected in double Ihh(-/-)/Gli3(-/-) mutants, signifying that Ihh action is normally modulated and delimited by Gli3 and Gli3(R) in particular. Both single and double mutants, however, failed to form an articular disc primordium, normally appreciable as an independent condensation between condylar apex and neighboring developing temporal bone in wild-type. This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin-expressing joint cavities. In summary, Ihh is very important for TMJ development, where it appears to regulate growth and elongation events, condylar cartilage phenotype, and chondroprogenitor cell function. Absence of articular disc and joint cavities in single and double mutants points to irreplaceable Ihh roles in formation of those critical TMJ components.

Links

PubMed Online version:10.1002/dvdy.21036

Keywords

Animals; DNA Primers; Gene Expression Regulation, Developmental; Hedgehog Proteins/metabolism; Hedgehog Proteins/physiology; In Situ Hybridization; Kruppel-Like Transcription Factors/metabolism; Mandibular Condyle/embryology; Mice; Mice, Knockout; Nerve Tissue Proteins/metabolism; Signal Transduction/physiology; Temporomandibular Joint/embryology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IHH

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1934258

P

Seeded From UniProt

complete

MOUSE:IHH

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95729

P

Seeded From UniProt

complete

MOUSE:IHH

acts_upstream_of_or_within

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1934258

P

Seeded From UniProt

complete

MOUSE:IHH

acts_upstream_of_or_within

GO:0072498: embryonic skeletal joint development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1934258

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0042127: regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96533

P

Seeded From UniProt

complete


See also

References

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