Wnt signaling in vetebrate limb and skeletal development

细胞-细胞信号传导是脊椎动物胚胎控制其发育的主要策略。我们感兴趣的是在脊椎动物胚胎发育，特别是肢体发育和骨骼形态发生的控制中，Wnt介导的主要信号通路的机制理解。在肢体发育的早期，包括Wnt家族成员在内的信号分子决定了晚期结构，即，骨架元素就会形成。肢体中的骨骼形态发生通过软骨内骨形成发生，其中软骨细胞（它们形成软骨）和成骨细胞（它们分泌骨基质）从间充质凝聚分化。随后是软骨细胞和成骨细胞的连续增殖和成熟，它们受到严格的调节和协调，以确保骨骼系统的正确形态发生。在过去的一年里，我们一直致力于该项目的四个方面：（1）Wnt 5a作为一个全球性的线索，在建立软骨细胞极性在伸长软骨中的作用。 (2)Wnt/PCP在软骨和骨发育中的作用及其机制 (3)Wnt信号调节肝干细胞自我更新和分化。(4)肝脏发育和肿瘤形成中的Wnt/Hippo信号通路

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.