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

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


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.

MeSH terms

  • Animals
  • Axon Guidance / physiology*
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • Discrimination, Psychological / physiology
  • Growth Cones / metabolism
  • Lysophospholipids / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Neural Pathways / metabolism
  • Neural Pathways / physiology
  • Phosphorylation
  • Signal Transduction / physiology*
  • Thalamus / growth & development*
  • Thalamus / metabolism


  • Cytoskeletal Proteins
  • Lysophospholipids
  • Membrane Proteins
  • Prg-2 protein, mouse
  • radixin
  • lysophosphatidic acid