Cytoskeleton club - Coralie Fassier

Speaker: Coralie Fassier - Institut de la Vision, Paris

Title: Microtubule-destabilizing enzymes in healthy and pathological development of neuronal circuits

Abstract: The mature nervous system is an intricate network in which precise connectivity between neurons is critical for the optimal functioning of the system. Neuronal connectivity is established during development by successive steps of axon outgrowth/navigation, synapse formation and pruning of exuberant connections and only undergoes limited remodelling in the mature nervous system. A crucial step in the assembly of neuronal circuits lies in the ability of axons to navigate accurately toward their appropriate targets. This complex task is achieved by the growth cone machinery, a cytoskeleton-based structure that senses extracellular guidance signals and translates them into growth cone mechanical behaviours. While microtubules recently emerged as key driving forces of growth cone steering, the numerous players that regulates microtubule remodelling in navigating axons, as well as their specific mode of action and regulation by guidance cues remain largely unknown. However, the exponentially growing number of neurodevelopmental disorders associated with mutations in genes encoding the microtubule building block (i.e., tubulin dimers), microtubule-modifying enzymes or -interacting proteins emphasizes the need to identify the protein networks that regulate microtubule functions in developing neurons. 
Over the last five years, my group has pioneered the use of multi-systemic approaches – including in vivo live imaging of cellular processes in navigating axons – to dissect the role of disease-related microtubule destabilizing enzymes in the wiring of neuronal circuits. We and others not only revealed the importance of microtubule composition/posttranslational modifications in fine-tuning microtubule functions in neuronal circuit wiring, but also unveiled the functional versatility of key microtubule interactors in such processes. Our work the highlights how decisive the tubulin code and MT-interactor diversity/versatility are in expanding the range of axon guidance behaviours and underlying neuronal connections that can be controlled by a limited repertoire of extracellular cues.