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 found that (1) Signaling through G proteins play important roles to modulate Wnt signaling activities both in normal development and in diseases;(2) Hippo signaling is required for liver organ size control and tumor suppression. Wnt signaling may act downstream of the Hippo signaling in liver tumorigenesis. (3) The Wnt/PCP pathway controls left-right asymmetry in early development.