Living Systems Institute, School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Yonglong Dang
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Gediminas Greicius
Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
Lilian Tamara Kaufmann
Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
Benedikt Prunsche
Institute of Applied Physics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Jakob Rosenbauer
John von Neumann Institute for Computing, Jülich Supercomputing Centre, Jülich, Germany
Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Karlsruhe, Germany; Institute of Imaging and Computer Vision, RWTH Aachen University, Aachen, Germany
Ralf Mikut
Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Suat Özbek
Centre of Organismal Studies, University of Heidelberg, Karlsruhe, Germany
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany; Institute of Applied Physics, Karlsruhe Institute of Technology, Karlsruhe, Germany; Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe, Germany; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, United States
Alexander Schug
John von Neumann Institute for Computing, Jülich Supercomputing Centre, Jülich, Germany; Steinbuch Centre for Computing, Karlsruhe Institute of Technology, Karlsruhe, Germany
Living Systems Institute, School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany
Signaling filopodia, termed cytonemes, are dynamic actin-based membrane structures that regulate the exchange of signaling molecules and their receptors within tissues. However, how cytoneme formation is regulated remains unclear. Here, we show that Wnt/planar cell polarity (PCP) autocrine signaling controls the emergence of cytonemes, and that cytonemes subsequently control paracrine Wnt/β-catenin signal activation. Upon binding of the Wnt family member Wnt8a, the receptor tyrosine kinase Ror2 becomes activated. Ror2/PCP signaling leads to the induction of cytonemes, which mediate the transport of Wnt8a to neighboring cells. In the Wnt-receiving cells, Wnt8a on cytonemes triggers Wnt/β-catenin-dependent gene transcription and proliferation. We show that cytoneme-based Wnt transport operates in diverse processes, including zebrafish development, murine intestinal crypt and human cancer organoids, demonstrating that Wnt transport by cytonemes and its control via the Ror2 pathway is highly conserved in vertebrates.
