Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
Research output: Contribution to journal › Journal article › Research › peer-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 & 7 others
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.
|Number of pages||17|
|Publication status||Published - 5 Oct 2016|