Wnt signaling in vetebrate limb and skeletal development

细胞-细胞信号是脊椎动物胚胎控制其发育的主要策略。我们感兴趣的是WNTS在控制脊椎动物胚胎发育，特别是肢体发育和骨骼形态发生中所介导的一个主要信号通路的机制。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，即骨骼元素将在哪里和何时形成。肢体的骨骼形态形成是通过软骨内成骨发生的，软骨细胞(它们形成软骨)和成骨细胞(它们分泌骨基质)是从间充质凝聚中分化出来的。紧随其后的是软骨细胞和成骨细胞的连续增殖和成熟，它们受到严格的调控和协调，以确保骨骼系统的适当形态发生。在过去的一年里，我们一直致力于该项目的四个方面：(1)Wnt5a作为全球线索在确定伸长软骨中软骨细胞极性方面的作用。(2)Wnt/PCP在软骨和骨发育中的作用及机制。(3)Wnt信号调节肝干细胞的自我更新和分化。(4)Wnt/Hippo信号通路在肝脏发育和肿瘤形成中的作用。

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.