Further Development 19.8: Joints Need Blood Vessels , Wnt proteins, and Working Muscles to Form

Development of the Tetrapod Limb

Blood vessels and Wnt proteins also appear to be critical in joint formation. The conversion of mesenchyme cells into nodules of cartilage-forming tissue establishes the bone boundaries. The mesenchyme will not form such nodules in the presence of blood vessels, and one of the first indications of cartilage formation is the regression of blood vessels in the region wherein the nodule will form (Yin and Pacifici 2001). Wnt proteins are critical in sustaining transcription of GDF5, and β-catenin produced by the Wnts is able to suppress the Sox9 and collagen-2 genes that characterize precartilage cells (Hartmann and Tabin 2001; Tufan and Tuan 2001).

Joints are not just absences of bone. Rather, joints are complex structures that incorporate a lubrication system, an immune system, and a ligament system, all joined to the proper articulation of the skeleton. One critical element of joint formation that allows this differentiation is muscle contraction. In normal joint formation, the cells that will form the joint lose their chondrocyte characteristics (such as expression of collagen 2 and Sox9) and instead begin to express GDF5, Wnt4, Wnt9a, and Ext1 (a protein necessary for synthesizing heparan sulfate). These cells will form the articulate cartilage and the synovium, which secretes lubricating synovial fluid (Koyama et al. 2008; Mundy et al. 2011). Kahn and colleagues (2009) have shown that the movement of the bones is necessary for maintaining this commitment to form joints. In mutant mice where the muscles do not form or are paralyzed, the joint cells revert back to a cartilaginous phenotype.)

Literature Cited

Hartmann, C. and C. J. Tabin. 2001. Wnt-14 plays a pivotal role in inducing synovial joint formation in the developing appendicular skeleton. Cell 104: 341–351.
PubMed Link

Kahn, J. and 11 others. 2009. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16: 734–743.
PubMed Link

Koyama, E. and 13 others. 2008. A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Dev. Biol. 316: 62–73.
PubMed Link

Mundy, C., T. Yasuda, T. Kinumatsu, Y. Yamaguchi, M. Iwamoto, M. Enomoto-Iwamoto, E. Koyama and M. Pacifici. 2011. Synovial joint formation requires local Ext1 expression and heparan sulfate production in developing mouse embryo limbs and spine. Dev. Biol. 351: 70–81.
PubMed Link

Tufan, A. C. and R. S. Tuan. 2001. Wnt regulation of limb mesenchymal chondrogenesis is accompanied by altered N-cadherin-related functions. FASEB J. 15: 1436–1438.
PubMed Link

Yin, M. and M. Pacifici. 2001. Vascular regression is required for mesenchymal condensation and chondrogenesis in the developing limb. Dev. Dyn. 222: 522–533.
PubMed Link

 

 

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