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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Jin Cheng
  • Sadhna Sahani
  • Torben Johann Hausrat
  • Jenq-Wei Yang
  • Haichao Ji
  • Nikolai Schmarowski
  • Heiko Endle
  • Xinfeng Liu
  • Yunbo Li
  • Rahel Böttche
  • Konstantin Radyushkin
  • Hans M Maric
  • Anna Hoerder-Suabedissen
  • Zoltán Molnár
  • Pierre-Hugues Prouvot
  • Thorsten Trimbuch
  • Olaf Ninnemann
  • Jisen Huai
  • Wei Fan
  • Barbara Visentin
  • Roger Sabbadini
  • Albrecht Stroh
  • Heiko J Luhmann
  • Matthias Kneussel
  • Robert Nitsch
  • Johannes Vogt

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 languageEnglish
Issue number1
Pages (from-to)126-142
Number of pages17
Publication statusPublished - 5 Oct 2016

ID: 167472377