Dataset Information

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.

SUBMITTER: Cheng J

PROVIDER: S-EPMC5065528 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Cheng Jin J Sahani Sadhna S Hausrat Torben Johann TJ Yang Jenq-Wei JW Ji Haichao H Schmarowski Nikolai N Endle Heiko H Liu Xinfeng X Li Yunbo Y Böttche Rahel R Radyushkin Konstantin K Maric Hans M HM Hoerder-Suabedissen Anna A Molnár Zoltán Z Prouvot Pierre-Hugues PH Trimbuch Thorsten T Ninnemann Olaf O Huai Jisen J Fan Wei W Visentin Barbara B Sabbadini Roger R Strømgaard Kristian K Stroh Albrecht A Luhmann Heiko J HJ Kneussel Matthias M Nitsch Robert R Vogt Johannes J

Neuron 20160915 1

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 towa ...[more]

PMID: 27641493

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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis

Dataset Information

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

Publications

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

Similar Datasets

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