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RNA expression data of embryonic E16.5 mouse temporomandibular joint (TMJ)

ABSTRACT: We conducted a genetic analysis of the developing temporo-mandibular 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 to other synovial joints including the shoulder joint and the hip joint. 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 utilized a conditional strategy to remove activity of the Hh co-receptor encoded by Smo 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE17473 | GEO | 2009/10/15

SECONDARY ACCESSION(S): PRJNA118717

REPOSITORIES: GEO

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Project description:The biological characteristics of the temporomandibular joint (TMJ) disc involve complex changes in cell identity and extracellular matrix (ECM) composition to modulate jaw function during postnatal growth and aging. To better understand this process, we profiled and analyzed 39111 single-cell transcriptomes of TMJ disc cells from mice at different postnatal stages. Our data showed that TMJ disc cells are composed of 9 distinct clusters that can be divided into 4 principal cell types: fibroblasts (FBs), which were the most abundant, endothelial cells (ECs), macrophages (MPhs) and mural cells (MCs). FBs were found to exhibit heterogeneity in terms of biological processes related to ECM secretion and metabolic functions. The ECs and MPhs mainly clustered together in the junction of the anterior disc band and anterior attachment, indicating the potential importance of the inflammatory response in this region in the pathological process of disc diseases. Notably, we found for the first time that resident MCs are the source of the progenitor niche in TMJ discs. The pseudotime trajectory showed that MCs have 2 lineage fates: self-renewal or multidirectional differentiation toward functional cells. In MCs, the NOTCH3 and THY1 signaling pathways were ubiquitously active at all stages, coupled with specific gene expression of Notch3 and Thy1 in MCs, indicating the critical role of these molecules in MC characteristics. As an example, THY1+ cells in TMJ discs showed markedly stronger stem cell characteristics than THY1- disc cells in vitro and ex vivo. In addition, lineage tracing in vivo showed that the Myh11-CreER+ MC lineage proliferated and migrated to coordinate angiogenesis during disc injury but gradually lost its progenitor characteristics and ultimately became a functional cell for disc repair. Overall, we reveal multiple insights into the coordinated and temporal development of TMJ disc cells at different postnatal stages and are the first to describe the resident MC progenitor cell niche during TMJ disc growth and injury.

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RNA expression data of embryonic E16.5 mouse temporomandibular joint (TMJ)

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