Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
| Autor: | Jisen Huai, Roger A. Sabbadini, Heiko Endle, Zoltán Molnár, Robert Nitsch, Jin Cheng, Olaf Ninnemann, Hans Michael Maric, Albrecht Stroh, Sadhna Sahani, Torben J. Hausrat, Heiko J. Luhmann, Jenq-Wei Yang, Pierre-Hugues Prouvot, Xinfeng Liu, Barbara Visentin, Matthias Kneussel, Thorsten Trimbuch, Nikolai Schmarowski, Wei Fan, Konstantin Radyushkin, Haichao Ji, Kristian Strømgaard, Yunbo Li, Rahel Böttche, Anna Hoerder-Suabedissen, Johannes Vogt |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neuroscience(all) Thalamus Growth Cones Sensory system Biology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Discrimination Psychological Radixin Lysophosphatidic acid Neural Pathways medicine Animals Phosphorylation Growth cone Cerebral Cortex Mice Knockout General Neuroscience Membrane Proteins Axon Guidance Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure chemistry Cerebral cortex Axon guidance Signal transduction Lysophospholipids Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuron |
| ISSN: | 1097-4199 0896-6273 |
| Popis: | Summary 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. Highlights • PRG-2 at the growth cone mediates axonal LPA sensitivity of thalamocortical fibers • LPA/PRG-2/RDX signaling in the growth cone is a novel axon guidance mechanism • PRG-2 deficiency disrupts precision of thalamocotrical somatotopy • PRG-2−/− mice have altered thalamocortical targeting and specific sensory defects Cheng et al. describe a new axon guidance mechanism depending on PRG-2 at the growth cone of thalamocortical axons and extracellular LPA synthesized below the cortical plate. Molecular analysis revealed LPA/PRG-2/RDX signaling at the growth cone important for thalamocortical targeting. |
| Databáze: | OpenAIRE |
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