Temporomandibular joint formation requires two distinct hedgehog-dependent steps.
We conducted a genetic analysis of the developing temporo-mandibular or temporomandi-bular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared with those of other synovial joints, including the shoulder and the hip joints. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth-plate-like cellular organization and no disk is formed. In addition, we used a conditional strategy to remove Smo, a positive effector of the Hh signaling pathway, from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ.
Purcell
Patricia
P
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Joo
Brian W
BW
Hu
Jimmy K
JK
Tran
Pamela V
PV
Calicchio
Monica L
ML
O'Connell
Daniel J
DJ
Maas
Richard L
RL
Tabin
Clifford J
CJ
D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D053823:Hedgehog Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D013704:Temporomandibular Joint / Q000196:embryology* / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2
C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000075746:Zinc Finger Protein Gli2