title: Filopodia-based Wnt transport during vertebrate tissue patterning.
abstract: Paracrine Wnt/β-catenin signalling is important during developmental processes, tissue regeneration and stem cell regulation. Wnt proteins are morphogens, which form concentration gradients across responsive tissues. Little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates. Here we show that Wnt8a is transported on actin-based filopodia to contact responding cells and activate signalling during neural plate formation in zebrafish. Cdc42/N-Wasp regulates the formation of these Wnt-positive filopodia. Enhanced formation of filopodia increases the effective signalling range of Wnt by facilitating spreading. Consistently, reduction in filopodia leads to a restricted distribution of the ligand and a limited signalling range. Using a simulation, we provide evidence that such a short-range transport system for Wnt has a long-range signalling function. Indeed, we show that a filopodia-based transport system for Wnt8a controls anteroposterior patterning of the neural plate during vertebrate gastrulation.
authors.affiliation: Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Eliana
authors.initials: E
authors.lastname: Stanganello
authors.affiliation: Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Anja I H
authors.initials: AI
authors.lastname: Hagemann
authors.affiliation: Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mattes
authors.affiliation: 1] Steinbuch Center for Computing (SCC), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany [2] Department of Physics, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Claude
authors.initials: C
authors.lastname: Sinner
authors.affiliation: Institute of Cell biology, ZMBE, University of Münster, 48149 Münster, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Meyen
authors.affiliation: Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Weber
authors.affiliation: Steinbuch Center for Computing (SCC), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schug
authors.affiliation: Institute of Cell biology, ZMBE, University of Münster, 48149 Münster, Germany.
authors.forename: Erez
authors.initials: E
authors.lastname: Raz
authors.affiliation: Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Scholpp
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D003198:Computer Simulation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D018613:Microscopy, Confocal; D054258:Neural Plate / Q000196:embryology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D016376:Oligonucleotides, Antisense; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094521:wnt8a protein, zebrafish; D020764:cdc42 GTP-Binding Protein