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Otx2-glycosaminoglycan interaction to regulate visual cortex plasticity

Abstract : During postnatal development of the visual cerebral cortex, Otx2 homeoprotein is transferred preferentially into parvalbumin inhibitory interneurons (PV-cells), induces their maturation and regulates a critical period of plasticity for binocular vision. During the critical period, PV-cells are gradually enwrapped by perineuronal nets enriched in glycosaminoglycans (GAGs), which are likely involved in the capture of Otx2. To understand how Otx2 interacts with GAGs at the surface of PV-cells for critical period regulation, we have analyzed a transgenic Otx2-AA mouse line in which the interaction between Otx2 and GAGs is disrupted. These mice show a reduced specificity of cortical Otx2 for PV-cells with concomitant delayed onset and closure of critical period for ocular dominance. We have also identified that Otx2 protein binds chondroitin sulfate chains of the perineuronal nets and that it has a high affinity for the chondroitin sulfate CS-E. We have therefore developed a sugar-ase protection assay for identifying specific glycan sequences involved in homeoprotein recognition. Throughout adulthood, the cortex receives Otx2 to maintain a consolidated, non-plastic state. To interfere with Otx2 transfer in the adult and reopen a window of plasticity, we have developed two models: a synthetic hexasaccharide analogue of CS-E that binds to Otx2 and an inducible, knock-in mouse allowing spatio-temporal control of a secreted single chain antibody against Otx2. All these results confirm and clarify the in vivo role for Otx2-GAG interaction, both in the timing of critical periods during postnatal development and in the maintenance of the non-plastic state of the cortex in the adult.
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Submitted on : Thursday, November 20, 2014 - 10:02:08 AM
Last modification on : Saturday, April 24, 2021 - 6:46:03 PM
Long-term archiving on: : Monday, February 23, 2015 - 8:45:24 AM


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  • HAL Id : tel-01084780, version 1


Clémence Francoise Bernard. Otx2-glycosaminoglycan interaction to regulate visual cortex plasticity. Neurons and Cognition [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2014. English. ⟨NNT : 2014PA066228⟩. ⟨tel-01084780⟩



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