title: Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling.
abstract: Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers. PRG-2 electroporation in the PRG-2-/-thalamus restored the aberrant cortical innervation. We identified radixin as a PRG-2 interaction partner and showed that radixin accumulation in growth cones and its LPA-dependent phosphorylation depend on its binding to specific regions within the C-terminal region of PRG-2. In vivo recordings and whisker-specific behavioral tests demonstrated sensory discrimination deficits in PRG-2-/-animals. Our data show that bioactive phospholipids and PRG-2 are critical for guiding thalamic axons to their proper cortical targets.
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sahani
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute for Molecular Neurogenetics, Center for Molecular Neurobiology Hamburg (ZMNH), 20251 Hamburg, Germany.
authors.forename: Torben Johann
authors.initials: TJ
authors.lastname: Hausrat
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany.
authors.forename: Jenq-Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Haichao
authors.initials: H
authors.lastname: Ji
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Schmarowski
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Endle
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Rahel
authors.initials: R
authors.lastname: Böttche
authors.affiliation: Focus Program Translational Neuroscience, Johannes Gutenberg University, 55128 Mainz, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.affiliation: Department of Drug Design and Pharmacology, Center for Biopharmaceuticals, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Hans M
authors.initials: HM
authors.lastname: Maric
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Hoerder-Suabedissen
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Pierre-Hugues
authors.initials: PH
authors.lastname: Prouvot
authors.affiliation: Institute for Cell Biology and Neurobiology, Charité, 10117 Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Trimbuch
authors.affiliation: Institute for Cell Biology and Neurobiology, Charité, 10117 Berlin, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Jisen
authors.initials: J
authors.lastname: Huai
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Lpath Inc., San Diego, CA 92121, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Visentin
authors.affiliation: Lpath Inc., San Diego, CA 92121, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Sabbadini
authors.affiliation: Department of Drug Design and Pharmacology, Center for Biopharmaceuticals, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Strømgaard
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stroh
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany.
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute for Molecular Neurogenetics, Center for Molecular Neurobiology Hamburg (ZMNH), 20251 Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kneussel
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. Electronic address: robert.nitsch@unimedizin-mainz.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. Electronic address: johannes.vogt@unimedizin-mainz.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000502:physiology*; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004192:Discrimination, Psychological / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism; D008246:Lysophospholipids / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development* / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D008246:Lysophospholipids; D008565:Membrane Proteins; C000623017:Prg-2 protein, mouse; C071776:radixin; C032881:lysophosphatidic acid