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Presenting Author(s) Yingzi Yang
Abstract Title Different Wnt signalling pathways exhibit distinct functions and signalling mechanisms in controlling cartilage development in the limb.
Full author List Xizhi Guo, Timothy Day, Lilia Topol, Xueyuan Jiang, Lisa Garrett-Beal and Yingzi Yang
Text of abstract Wnt signalling pathways play critical roles in regulating different aspects of skeletal morphogenesis. We have studied the function and signalling mechanism of several different Wnt pathways in controlling cartilage development in the developing long bones in the limb through combined approaches of mouse genetics, cell biology and organ cultures. By analysing the skeletal development defects in the Wnt5a-/- mouse embryos, we have shown that at early stages of skeletal morphogenesis, Wnt5a signalling is required for chondrogenesis in the distal limb bud. We further showed that Wnt5a does so by inhibiting the chondrogenic-inhibitory activity of the b-catenin-mediated canonical Wnt signalling through promoting b-catenin degradation in a GSK3-indpendent manner. We have also generated transgenic mice that express Wnt5a in proliferative chondrocytes. Combined with the analysis of the Wnt5a-/- cartilage, we found that in the formed cartilage, Wnt5a signalling maintains the resting zone of the cartilage and is also required for chondrocyte hypertrophy by promoting cell cycle exit. Interestingly, Wnt5b, the closest family member of Wnt5a, exhibit different activity and it delays chondrocyte hypertrophy by preventing cell cycle exit. However, neither Wnt5a nor Wnt5b signals through the b-catenin-mediated canonical Wnt signalling in the developing cartilage because expression of a constitutively active form of b-catenin in proliferative chondrocytes resulted in a completely different phenotype. Moreover, we have demonstrated for the first time that the b-catenin-mediated canonical Wnt signalling is the only signalling pathway identified so far that is both sufficient and necessary for synovial joint induction. We will discuss this part of our work in more detail.
Which session is your work most relevant to: Tissue differentiation