Wnt signaling in vetebrate limb and skeletal development

National Human Genome Research Institute

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Abstract

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. In the past year, we have being working on four aspects of the project: (1) The role of Wnt5a as a global cue in establishing chondrocyte polarity in the elongating cartilage. (2) The roles and mechanisms of Wnt/PCP in cartilage and bone development. (3) Wnt signaling regulates liver stem cell self renewal and differentiation. (4) The Wnt/Hippo signaling pathway in liver development and tumor formation.