Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling
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 PR...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2016
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| _version_ | 1826256619838636032 |
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| author | Cheng, J Sahani, S Hausrat, T Yang, J Ji, H Schmarowski, N Endle, H Liu, X Li, Y Böttche, R Radyushkin, K Maric, H Hoerder-Suabedissen, A Molnár, Z Prouvot, P Trimbuch, T Ninnemann, O Huai, J Fan, W Visentin, B Sabbadini, R Strømgaard, K Stroh, A Luhmann, H Kneussel, M Nitsch, R Vogt, J |
| author_facet | Cheng, J Sahani, S Hausrat, T Yang, J Ji, H Schmarowski, N Endle, H Liu, X Li, Y Böttche, R Radyushkin, K Maric, H Hoerder-Suabedissen, A Molnár, Z Prouvot, P Trimbuch, T Ninnemann, O Huai, J Fan, W Visentin, B Sabbadini, R Strømgaard, K Stroh, A Luhmann, H Kneussel, M Nitsch, R Vogt, J |
| author_sort | Cheng, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:05:07Z |
| format | Journal article |
| id | oxford-uuid:012e7654-e3f2-4fc0-bd28-fb00e48001c8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:05:07Z |
| publishDate | 2016 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:012e7654-e3f2-4fc0-bd28-fb00e48001c82022-03-26T08:33:32ZPrecise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signalingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:012e7654-e3f2-4fc0-bd28-fb00e48001c8EnglishSymplectic Elements at OxfordCell Press2016Cheng, JSahani, SHausrat, TYang, JJi, HSchmarowski, NEndle, HLiu, XLi, YBöttche, RRadyushkin, KMaric, HHoerder-Suabedissen, AMolnár, ZProuvot, PTrimbuch, TNinnemann, OHuai, JFan, WVisentin, BSabbadini, RStrømgaard, KStroh, ALuhmann, HKneussel, MNitsch, RVogt, JPrecise 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. |
| spellingShingle | Cheng, J Sahani, S Hausrat, T Yang, J Ji, H Schmarowski, N Endle, H Liu, X Li, Y Böttche, R Radyushkin, K Maric, H Hoerder-Suabedissen, A Molnár, Z Prouvot, P Trimbuch, T Ninnemann, O Huai, J Fan, W Visentin, B Sabbadini, R Strømgaard, K Stroh, A Luhmann, H Kneussel, M Nitsch, R Vogt, J Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title | Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title_full | Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title_fullStr | Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title_full_unstemmed | Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title_short | Precise somatotopic thalamocortical axon guidance depends on LPA-mediated PRG-2/radixin signaling |
| title_sort | precise somatotopic thalamocortical axon guidance depends on lpa mediated prg 2 radixin signaling |
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