Role of canonical Wnt-signalling in joint formation

Später, Daniela; Hill, Theo P.; Gruber, Michaela; Hartmann, Christine

doi:10.22203/ecm.v012a09

Cited by 95 publications

(82 citation statements)

References 18 publications

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“…Conversely, a large number of genes are induced specifically in the location of the future joint. Prominent among these are Wnt9a (formerly called Wnt14), a canonical Wnt ligand (9)(10)(11), and depending on the specific joint, Gdf5, Gdf6, or Gdf7, members of the BMP/TGF␤ superfamily (12)(13)(14)(15). Strikingly, these genes are expressed during and act in the formation of joints that form between the long bones by segmentation and in other classes of joints such as those between vertebrae and those between calvarial membranous bones.…”

mentioning

confidence: 99%

Temporomandibular joint formation requires two distinct hedgehog-dependent steps

Purcell

Joo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

126

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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.

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mentioning

confidence: 99%

Temporomandibular joint formation requires two distinct hedgehog-dependent steps

Purcell

Joo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

126

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“…Ectopic expression of Wnt9a (previously called Wnt14), another early marker of the interzone, can direct ectopic joint formation in developing mouse and chick limbs (Hartmann and Tabin, 2001;Guo et al, 2004). However, Wnt signaling is not required for the induction but for the subsequent maintenance of the fate of joint interzone cells by actively suppressing their chondrogenic potential to allow joint formation (Spater et al, 2006). The interaction of these signaling pathways appears to be coordinated within the interzone by heparin sulfate proteoglycans to assure proper joint morphogenesis (Mundy et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of synovial joints: Use of microarray analysis to identify factors that direct the development of the knee and elbow

Pazin

Gamer

Cox

et al. 2012

Developmental Dynamics

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Background: Synovial joints develop from the interzone, a dense layer of mesenchymal progenitor cells that marks the site of the future joint. During the morphogenic events that follow, joints attain their distinct shape and organization. The molecular mechanisms controlling the initial specification of synovial joints has been studied, but the question of how individual joints attain the specific structure required for their unique functions remains largely unresolved. Here, we use microarray analysis to compare knee and elbow formation to identify factors involved in the development of specific joints. Results: The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor-beta/bone morphogenetic protein (TGFb/BMP) and Wnt signaling. Consistent with these findings, we show that TGFb signaling directs knee morphogenesis, and is necessary for meniscus development. The tissue surrounding the elbow is highly enriched for genes involved in muscle specification and differentiation, and in splotch-delayed muscleless mutants, elbow, but not knee morphogenesis is disrupted. Conclusions: Our results suggest there are fundamental differences in how individual joints develop after interzone formation. Our microarray analyses provides a new resource for further investigation of the pathways involved in the morphogenesis of specific synovial joints.

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“…Genetic deletion of Wnt9a in mice did not affect the expression of joint marker genes, but it resulted in synovial chondroid metaplasia in some joints; and the joint phenotype was enhanced in the double knockout embryos of Wnt9a and Wnt4 (Spater et al 2006a, b). Conditional deletion of b-catenin by Col2a1-Cre in mesenchymal/chondrocyte lineage cells did not diminish but upregulated the expression domain of the early joint marker genes including Gdf5, Wnt4, and Gli1 (Spater et al 2006a). Together, these data suggest that Wnt4 and Wnt9a act cooperatively during joint development to control the fate of the joint interzone cells, possibly acting through the canonical Wnt/b-catenin signaling pathway.…”

Section: Resultsmentioning

confidence: 91%

“…The presumptive joint interzone is distinguishable around E12.5 in the mouse forelimbs with down-regulated expression of a chondrocyte marker Col2a1 and the clustered high expression of the joint markers Gdf5 and Wnt4 in the future joint region (Spater et al 2006a). At this early age, X-gal staining for TOPgal activity was detected intensively in the chondrogenic condensation of the scapula, humerus, ulna, and radius (Fig.…”

Section: Resultsmentioning

confidence: 95%

Canonical Wnt signaling activity during synovial joint development

2009

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Wnt signaling plays important roles in skeletal development. However, the activation and function of canonical Wnt signaling in joint development remains unclear. We analyzed the lineage identity and developmental changes of the Wnt-responsive cells during synovial joint formation as well as adulthood in the Wnt signaling reporter TOPgal transgenic mice. At embryonic day (E) 12.5, we found that the TOPgal was inactivated in the presumptive joint forming interzone, but it was intensively activated in the cartilage anlage of developing long bones and digits. At E14.5, the TOPgal activity was found in a subgroup of the articular chondrocyte lineage cells, which were co-immunolabeled with Doublecortin intensively and with Vinculin weakly. At E18.5, the TOPgal/ Doublecortin co-immunolabeled cells were found in the superficial layer of the developing articular cartilage. During postnatal development, the TOPgal(?) articular chondrocytes were abundant at P7 and decreased from P10. A small number of TOPgal(?) articular chondrocytes were also found in adult joints. Our study suggests an age-and lineage-specific role of canonical Wnt signaling in joint development and maintenance.

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Role of canonical Wnt-signalling in joint formation

Cited by 95 publications

References 18 publications

Temporomandibular joint formation requires two distinct hedgehog-dependent steps

Temporomandibular joint formation requires two distinct hedgehog-dependent steps

Molecular profiling of synovial joints: Use of microarray analysis to identify factors that direct the development of the knee and elbow

Canonical Wnt signaling activity during synovial joint development

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