Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system

Noemie Vilallongue, Julia Schaeffer, Anne-Marie Hesse, Céline Delpech, Béatrice Blot, Antoine Paccard, Elise Plissonnier, Blandine Excoffier, Yohann Couté, Stephane Belin and Homaira Nawabi ()
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Noemie Vilallongue: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Julia Schaeffer: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Anne-Marie Hesse: University Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048
Céline Delpech: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Béatrice Blot: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Antoine Paccard: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Elise Plissonnier: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Blandine Excoffier: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Yohann Couté: University Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048
Stephane Belin: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences
Homaira Nawabi: University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract In the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of the proper target regions of regenerative axons is essential to uncover the modalities of adult reinnervation. In this study, we use mass spectrometry (MS)-based quantitative proteomics to address the proteomes of major nuclei of the adult visual system. These analyses reveal that guidance-associated molecules are expressed in adult visual targets. Moreover, we show that bilateral optic nerve injury modulates the expression of specific proteins. In contrast, the expression of guidance molecules remains steady. Finally, we show that regenerative axons are able to respond to guidance cues ex vivo, suggesting that these molecules possibly interfere with brain target reinnervation in adult. Using a long-distance regeneration model, we further demonstrate that the silencing of specific guidance signaling leads to rerouting of regenerative axons in vivo. Altogether, our results suggest ways to modulate axon guidance of regenerative neurons to achieve circuit repair in adult.

Date: 2022
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DOI: 10.1038/s41467-022-33799-4

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