Susman, Michael WKaruna, Edith PKunz, RyanGujral, Taranjit SCantú, Andrea VChoi, Shannon SJong, Brigette YOkada, KyokoScales, Michael KHum, JennieHu, LindaKirschner, MarcNishinakamura, RyuichiYamada, SoichiroLaird, Diana JJao, Li-EnGygi, StevenGreenberg, MichaelHo, Hsin-Yi Henry2017-12-052017Susman, M. W., E. P. Karuna, R. C. Kunz, T. S. Gujral, A. V. Cantú, S. S. Choi, B. Y. Jong, et al. 2017. “Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates.” eLife 6 (1): e26509. doi:10.7554/eLife.26509. http://dx.doi.org/10.7554/eLife.26509.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34491876Wnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin superfamily protein Kif26b as a downstream target of the Wnt5a-Ror pathway. Wnt5a-Ror, through a process independent of the canonical Wnt/β-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitin-proteasome system. Through this mechanism, Kif26b modulates the migratory behavior of cultured mesenchymal cells in a Wnt5a-dependent manner. Genetic perturbation of Kif26b function in vivo caused embryonic axis malformations and depletion of primordial germ cells in the developing gonad, two phenotypes characteristic of disrupted Wnt5a-Ror signaling. These findings indicate that Kif26b links Wnt5a-Ror signaling to the control of morphogenetic cell and tissue behaviors in vertebrates and reveal a new role for regulated proteolysis in noncanonical Wnt5a-Ror signal transduction.en-USnoncanonical Wnt signalingRorsignal transductiontissue morphogenesisregulated proteolysisKif26bMouseJournal Article2017-12-0510.7554/eLife.26509