Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
| العنوان: | Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling |
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| المؤلفون: | 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 |
| المصدر: | Neuron |
| بيانات النشر: | Cell Press, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1097-4199 0896-6273 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::663c20cb2aae7ed8aa2abc2c76dbee8eTest http://europepmc.org/articles/PMC5065528Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....663c20cb2aae7ed8aa2abc2c76dbee8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974199 08966273 |
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