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RESEARCH PRODUCT

Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling

Jisen HuaiRoger A. SabbadiniHeiko EndleZoltán MolnárRobert NitschJin ChengOlaf NinnemannHans Michael MaricAlbrecht StrohSadhna SahaniTorben J. HausratHeiko J. LuhmannJenq-wei YangPierre-hugues ProuvotXinfeng LiuBarbara VisentinMatthias KneusselThorsten TrimbuchNikolai SchmarowskiWei FanKonstantin RadyushkinHaichao JiKristian StrømgaardYunbo LiRahel BöttcheAnna Hoerder-suabedissenJohannes Vogt

subject

0301 basic medicineNeuroscience(all)ThalamusGrowth ConesSensory systemBiologyArticle03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicineDiscrimination PsychologicalThalamusRadixinLysophosphatidic acidNeural PathwaysmedicineAnimalsPhosphorylationGrowth coneCerebral CortexMice KnockoutGeneral NeuroscienceMembrane ProteinsAxon GuidanceCytoskeletal Proteins030104 developmental biologymedicine.anatomical_structurechemistryCerebral cortexAxon guidanceSignal transductionLysophospholipidsNeuroscience030217 neurology & neurosurgerySignal Transduction

description

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.

yearjournalcountryeditionlanguage
2016-10-01Neuron
10.1016/j.neuron.2016.08.035http://europepmc.org/articles/PMC5065528