Muenke syndrome is characterized by various craniofacial deformities and is 
caused by an autosomal-dominant activating mutation in fibroblast growth factor 
receptor 3 (FGFR3(P250R) ). Here, using mice carrying a corresponding mutation 
(FgfR3(P244R) ), we determined whether the mutation affects temporomandibular 
joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was 
expressed in condylar chondroprogenitors and maturing chondrocytes that also 
expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 
1(Ptch1). In FgfR3(P244R) mutants, the condyles displayed reduced levels of Ihh 
expression, H4C-positive proliferating chondroprogenitors, and collagen type II- 
and type X-expressing chondrocytes. Primary bone spongiosa formation was also 
disturbed and was accompanied by increased osteoclastic activity and reduced 
trabecular bone formation. Treatment of wild-type condylar explants with 
recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in 
superficial/polymorphic layers and proliferation in chondroprogenitors. We also 
observed early degenerative changes of condylar articular cartilage, abnormal 
development of the articular eminence/glenoid fossa in the TMJ, and fusion of 
the articular disc. Analysis of our data indicates that the activating 
FgfR3(P244R) mutation disturbs TMJ developmental processes, likely by reducing 
hedgehog signaling and endochondral ossification. We suggest that a balance 
between FGF and hedgehog signaling pathways is critical for the integrity of TMJ 
development and for the maintenance of cellular organization.