In this research project, we have found that; (1) activation of Wnt5a-Ror2 signaling occurs at a restricted region within the metanephric mesenchyme (MM), resulting in secretion of GDBF from the MM and subsequent activation of Ret at a restricted region on the Wölffian ducts (WD), eventually leading to the proper formation of the ureteric buds from the WD, which undergoes tubulogenesis and branching during the development of the kidneys, and that Wnt5a-Ror2/Ror1 signaling regulates cooperatively the formation of the MM at the proper position.; (2) during kidney fibrosis, induced by unilateral ureter obstruction, Wnt5a-Ror2 signaling is activated following epithelial-mesenchymal transition of renal tubular epithelial cells, and as a result epithelial basement membranes are destructed via matrix metalloproteinase-2 (MMP-2), induced by Wnt5a-Ror2 signaling.; (3) Wnt5a-Ror signaling plays important roles in the maintenance of stemness of neural progenitor cells through Dishevelled during the development of the cerebral neocortex.; (4) IFT20 (intraflagellar transport 20), a critical component of the ciliogenesis, is induced by Wnt5a-Ror2 siganling in osteosarcoma cells, and plays important roles in invadopodia formation and invasiveness of osteosarcoma cells by regulating polarity and structure of the Golgi apparatus (unpublished data).; (5) Wnt5a-Ror2 signaling in mesenchymal stem cells regulate the expression of CXCL16, thereby regulating the proliferation of cancer cells which express CXCR6.; and (6) Wnt5a-Ror2 signaling as well as Dok-family adaptors play crucial roles in maintaining homeostasis of epithelial tissues of the guts. We are also planning to study the role of Wnt5a-Ror2 signaling in age-related and/or inflammation-induced alterations of epithelial tissues of the salivary glands.