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

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; Kristian Strømgaard; Albrecht Stroh; Heiko J Luhmann; Matthias Kneussel; Robert Nitsch; Johannes Vogt

doi:10.1016/j.neuron.2016.08.035

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

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 VisentinRoger Sabbadini, Kristian Strømgaard, Albrecht Stroh, Heiko J Luhmann, Matthias Kneussel, Robert Nitsch, Johannes Vogt

32 Citations (Scopus)

Abstract

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 language	English
Journal	Neuron
Volume	92
Issue number	1
Pages (from-to)	126-142
Number of pages	17
ISSN	0896-6273
DOIs	https://doi.org/10.1016/j.neuron.2016.08.035
Publication status	Published - 5 Oct 2016

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Cheng, J., Sahani, S., Hausrat, T. J., Yang, J.-W., Ji, H., Schmarowski, N., Endle, H., Liu, X., Li, Y., Böttche, R., Radyushkin, K., Maric, H. M., Hoerder-Suabedissen, A., Molnár, Z., Prouvot, P.-H., Trimbuch, T., Ninnemann, O., Huai, J., Fan, W., ... Vogt, J. (2016). Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling. Neuron, 92(1), 126-142. https://doi.org/10.1016/j.neuron.2016.08.035

Cheng, J, Sahani, S, Hausrat, TJ, Yang, J-W, Ji, H, Schmarowski, N, Endle, H, Liu, X, Li, Y, Böttche, R, Radyushkin, K, Maric, HM, Hoerder-Suabedissen, A, Molnár, Z, Prouvot, P-H, Trimbuch, T, Ninnemann, O, Huai, J, Fan, W, Visentin, B, Sabbadini, R, Strømgaard, K, Stroh, A, Luhmann, HJ, Kneussel, M, Nitsch, R & Vogt, J 2016, 'Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling', Neuron, vol. 92, no. 1, pp. 126-142. https://doi.org/10.1016/j.neuron.2016.08.035

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title = "Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling",

abstract = "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.",

author = "Jin Cheng and Sadhna Sahani and Hausrat, {Torben Johann} and Jenq-Wei Yang and Haichao Ji and Nikolai Schmarowski and Heiko Endle and Xinfeng Liu and Yunbo Li and Rahel B{\"o}ttche and Konstantin Radyushkin and Maric, {Hans M} and Anna Hoerder-Suabedissen and Zolt{\'a}n Moln{\'a}r and Pierre-Hugues Prouvot and Thorsten Trimbuch and Olaf Ninnemann and Jisen Huai and Wei Fan and Barbara Visentin and Roger Sabbadini and Kristian Str{\o}mgaard and Albrecht Stroh and Luhmann, {Heiko J} and Matthias Kneussel and Robert Nitsch and Johannes Vogt",

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AU - Cheng, Jin

AU - Sahani, Sadhna

AU - Hausrat, Torben Johann

AU - Yang, Jenq-Wei

AU - Ji, Haichao

AU - Schmarowski, Nikolai

AU - Endle, Heiko

AU - Liu, Xinfeng

AU - Li, Yunbo

AU - Böttche, Rahel

AU - Radyushkin, Konstantin

AU - Maric, Hans M

AU - Hoerder-Suabedissen, Anna

AU - Molnár, Zoltán

AU - Prouvot, Pierre-Hugues

AU - Trimbuch, Thorsten

AU - Ninnemann, Olaf

AU - Huai, Jisen

AU - Fan, Wei

AU - Visentin, Barbara

AU - Sabbadini, Roger

AU - Strømgaard, Kristian

AU - Stroh, Albrecht

AU - Luhmann, Heiko J

AU - Kneussel, Matthias

AU - Nitsch, Robert

AU - Vogt, Johannes

PY - 2016/10/5

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N2 - 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.

AB - 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.

U2 - 10.1016/j.neuron.2016.08.035

DO - 10.1016/j.neuron.2016.08.035

M3 - Journal article

C2 - 27641493

SN - 0896-6273

VL - 92

SP - 126

EP - 142

JO - Neuron

JF - Neuron

IS - 1

ER -

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

Abstract

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