Wnt signaling in development and disease

One of the most remarkable biological processes is the formation of a morphologically complex and functional diverse multicellular organism such as a human being from a single fertilized egg within a short period of time. During this tightly regulated process of embryonic morphogenesis, functional tissues and organs are formed and they have to be properly maintained during adult lives. Because cell-cell signaling plays essential and pivotal roles in both embryonic development and adult physiology, understanding the function and the underlying molecular mechanism of key cell signaling pathways in both development and diseases has been a major focus of our lab. Here we primarily focus on Wnt signaling in major developmental events of the skeletal system.Wnts are evolutionarily conserved major regulatory factors in both development and disease. Wnt signaling is required in most embryonic developmental processes in both invertebrates and vertebrates. Abnormal Wnt signaling causes many types of tumors [1-3]. For instance, ectopic activation of Wnt1 gene expression in the mouse mammary gland leads to tumor formation [4]. Mutations in Wnt signaling components have also been found to cause other human diseases. Weakened Wnt/β-catenin signaling leads to osteoporosis-pseudoglioma syndrome due to reduced bone mass [5] whereas enhanced Wnt/β-catenin signaling causes thick bone syndrome due to increased bone mass [6,7]. In addition, Robinow syndrome and Brachydactyly Type B1 that are characterized by shortened skeletal elements are caused by mutations in the Wnt/planar cell polarity pathway components [8-11].Wnts are a large family of secreted molecules that can signal through several distinct pathways (Figure？1). The β-catenin mediated Wnt/β-catenin pathway is also called the canonical pathway. This pathway is best understood and mainly controls cell proliferation and differentiation. Central to this pathway is the control of β-catenin stability. In the absence of Wnt signaling