Molecular mechanisms in development and repair of the central nervous system
Julia Schaeffer
PI Local translation in axon regeneration
Group “Forever fit ? Preserving & repairing the body throughout life” IBDM, Marseille

Résumé
In the adult mammalian central nervous system (CNS), neurons fail to spontaneously regrow their axon after injury, which is the primary limiting step that prevents functional reconnection. This leads to an irreversible loss of sensory-motor and cognitive functions in patients affected by neurologic disorders.
To address this failure of axon regeneration, the field has investigated multiple aspects encompassing extrinsic mechanisms (external growth inhibitory cues, guidance defects) and intrinsic properties (regulation of gene expression, epigenetic remodelling, cytoskeletal and metabolic changes). In this line, my recent work has shown that the neuronal regrowth capacity depends on the translation of specific mRNAs into proteins, and that this process is controlled by association of regulatory factors with ribosomes, the functional units of protein synthesis.
Furthermore, it is now established that translation is spatially compartmentalized in neurons and also occurs locally in the axon. Axonal translation of specific subsets of mRNAs is critical for many steps of neural circuit development, and, as recently evidenced, for synaptic function and plasticity in the intact adult CNS. However, little is known about the role and parameters of local translation in regrowth of adult CNS axons after injury.
Here, I will discuss our current understanding of the mechanisms underlying the failure of adult CNS regeneration and the current strategies to promote axon regrowth after injury, using the gold standard model of optic nerve injury and the adult mouse retina. I will present the rationale for exploring local translation in injured axons as a way to promote axon regrowth and reconnection in the adult injured CNS.

Bio
I obtained my PhD in 2018 at the Univ. of Cambridge, UK, under the supervision of Roger Keynes, where I studied mechanisms of axon guidance for spinal nerve patterning during embryogenesis.
Then I came back to France for my post-doc, at the Grenoble Institute of Neurosciences. In collaborative projects between the teams led by Homaira Nawabi and Stephane Belin, I studied axon regeneration in the adult visual system, from promoting axon regrowth to repairing neuronal circuits.
Based on my PhD and post-doc experiences, I decided to explore local regulation of gene expression in the axon as a signature of its regrowth capacity. For this, I started my own research group at the IBDM in November 2024, with a primary research focus on molecular mechanisms of local protein synthesis in injured and regenerating axons of the adult retina.

Invitée par Neuroschool

Lundi 27 Janvier 2025 à 11h – Salle de conférence de l’Inmed

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