What makes neurons of the adult mammalian central nervous system (CNS) unable to regenerate their axon after injury?

Our lab investigates molecular mechanisms underlying axon regeneration, with a specific focus on local translation of mRNAs into proteins in the axon. Indeed, neurons are highly polarized cells that rely on local protein synthesis to rapidly adapt gene expression in distal compartments such as the axon. The contribution of axonal translation is actively explored in embryonic neuronal growth and in the peripheral nervous system, in which injured neurons can regenerate spontaneously.

In contrast, less is known about how axonal translation may contribute to axon regrowth in the injured CNS. So how is translation regulated locally in injured CNS axons? What are the key mechanisms of local translation required to trigger and sustain CNS axon regrowth (axonal localization and translation of specific mRNAs, axonal supply of ribosomes)? Can we manipulate these mechanisms to promote CNS axon regrowth, and ultimately tackle all steps of circuit reconnection after injury?

To address these questions, we study mouse retinal ganglion cells and their response to optic nerve injury as a paradigm of CNS injury and regeneration. In combination with techniques of subcellular compartmentalization, we use cutting-edge translatome analysis and dynamic imaging of translation events specifically in the axon, as well as functional testing in vivo.

Our approach leads us to address the features of local translation as a key to unlock CNS axon regeneration, including the intrinsic regrowth potential, the response to external cues and the neuronal subpopulation specificity.

More generally, our research addresses gene regulation in the axon as a signature of its specification, regrowth capacity and maintenance in response to injury.