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Neuron. 2016 Oct 5;92(1):126-142. doi: 10.1016/j.neuron.2016.08.035. Epub 2016 Sep 15.

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

Author information

1
Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
2
University Medical Center Hamburg-Eppendorf, Institute for Molecular Neurogenetics, Center for Molecular Neurobiology Hamburg (ZMNH), 20251 Hamburg, Germany.
3
Institute of Physiology, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany.
4
Focus Program Translational Neuroscience, Johannes Gutenberg University, 55128 Mainz, Germany.
5
Department of Drug Design and Pharmacology, Center for Biopharmaceuticals, University of Copenhagen, 2100 Copenhagen, Denmark.
6
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
7
Institute for Cell Biology and Neurobiology, Charité, 10117 Berlin, Germany.
8
Lpath Inc., San Diego, CA 92121, USA.
9
Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. Electronic address: robert.nitsch@unimedizin-mainz.de.
10
Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. Electronic address: johannes.vogt@unimedizin-mainz.de.

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.

PMID:
27641493
PMCID:
PMC5065528
DOI:
10.1016/j.neuron.2016.08.035
[Indexed for MEDLINE]
Free PMC Article

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