Cell-cell signaling is a major strategy that vertebrate embryos employ to control their development. We are interested in the mechanistic understanding of a major signaling pathway mediated by Wnts in the control of vertebrate embryonic development, in particular, limb development and skeletal morphogeneis. Early in limb development, signaling molecules which include the Wnt family members determine where and when the late structures, i.e., skeletal elements will form. Skeletal morphogeneis in the limb occurs through endochondral bone formation in which chondrocytes (they form the cartilage) and osteoblasts (they secrete bone matrix) are differentiated from mesenchymal condensations. This is followed by sequential proliferation and maturation of both chondrocytes and osteoblasts, which are tightly regulated and coordinated to ensure proper morphogenesis of the skeletal system. Apart from Wnt signlaing pathways, other signaling pathways such PTHrP also plays a crtical role in regulating chondrocyte hypertophy, a process required for endochondral bone formation. To understand the molecular mechanism whereby Wnt signaling regulates chondrocyte hypertrophy and maturation, in the past year, we have investigated the interplay between signaling pathways of Wnt and PTHrP in controlling chondrocyte hypertrophy through analyzing mutant mice in which Wnt and PTHrP signaling components are either inactivated or ectopically expressed, we have uncovered that PTHrP signaling acts downstream of Wnt signlaing in regulating chondrocyte hypetrophy. Furthermore, we found that Wnt signlaing regulates the final maturation of hypertrophic chondrocytes independently of PTHrP signaling.
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