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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.

Original publication

DOI

10.1016/j.neuron.2016.08.035

Type

Journal article

Journal

Neuron

Publication Date

05/10/2016

Volume

92

Pages

126 - 142

Keywords

Animals, Axon Guidance, Cerebral Cortex, Cytoskeletal Proteins, Discrimination (Psychology), Growth Cones, Lysophospholipids, Membrane Proteins, Mice, Mice, Knockout, Neural Pathways, Phosphorylation, Signal Transduction, Thalamus