Centre Broca Nouvelle-Aquitaine
Axon Guidance during mature CNS regeneration
Abstract
Mature neurons from the central nervous system are not able to regenerate after an insult. Therefore, patients have to bear motor and or cognitive disabilities for the rest of their lives as no treatment is available.
Many efforts have been deployed to understand this discrepancy. For over 20 years it has been thought that the CNS environment was the main cause of this lack of regeneration. Indeed, after CNS injury, myelin debris release and glia scar formation act as a chemical and physical barrier for axon outgrowth. Surprisingly their modulation in vivo did not unlock CNS repair. Since 2008, it has been shown that neurons themselves loose the ability to regenerate over the course of development. We showed that this capacity is further decreased by the injury itself. Thus, by modulating the neuronal intrinsic molecular pathways we are now able to induce long distance regeneration. However, another unexpected roadblock stands on the way to achieve functional recovery: regenerating axons present strong guidance defects that counteract any attempt to build a functional circuit. By using the model of the optic nerve and the visual system our lab aims to understand axon guidance mechanism in mature CNS during regeneration.
Selected publications
1– Vilallongue N, Schaeffer J, Hesse AM, Delpech C, Paccard A Couté Y, Belin S, Nawabi H. Axon guidance modalities in CNS regeneration revealed by quantitative proteomic analysis. BioRxive 2021 (doi: https://doi.org/10.1101/2021.03.26.437129)
2– SchaefferJ*, Delpech C*, Albert F, Belin S, Nawabi H. Adult mouse retina explants: an ex vivo window to explore central nervous system diseases. * co first autors; co–lead. Frontiers in Molecular Neuroscience 2020
3– Sonoda T, Li JY, Hayes NW, Chan JC, Okabe Y, Belin S, Nawabi H, Schmidt TM. A noncanonical inhibitory circuit dampens behavioral sensitivity to light. Science 2020
4– Nawabi H*, Belin S*, Cartoni R*, Williams PR, Wang C, Latremolière A, Wang X, Zhu J, Taub DG, Fu X, Yu B, Gu X, Woolf CJ, Liu JS, Gabel CV, Steen JA, He Z. Doublecortin–Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Neuron 2015 Nov 18;88(4):704–19. *equal contribution
5– Belin S* Nawabi H*, Wang C, Tang S, Latremoliere A, Warren P, Schorle H, Uncu C, Woolf CJ, He Z, Steen JA. Injury–induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Neuron 2015 May 20;86(4):1000–14.) *equal contribution. Article cited as Editor’s choice in Science Signaling 26 May 2015 Vol.8 issue378
Organized by Bordeaux Neurocampus, NBA and Bordeaux Neurocampus Graduate Program
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