We are pleased to welcome Coralie FASSIER, from the Vision Institute of Paris, on February 20th who is invited by Pascale BOMONT.
She will give a seminar at 11am entitled: “Microtubule-destabilizing enzymes in heathy and pathological development of neuronal circuits”.
The seminar will be in the Amphi Hermann, 1st floor.
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.
Brief CV:
Throughout my career, my scientific interest has always been focused on the cellular and molecular mechanisms underlying the establishment and maintenance of neuronal circuits, with a special focus on two tightly related cellular processes frequently altered in neurological disorders: cytoskeleton dynamics and membrane trafficking. During my PhD in J. Melki’s lab and my subsequent post-doc in J. Hazan‘s team, my research work mainly aimed at deciphering the molecular mechanisms triggering axonal degeneration in Hereditary Spastic Paraplegia (HSP) caused by mutations in the microtubule-severing enzyme spastin and the membrane-trafficking protein Atlastin through the generation of mouse, zebrafish and cellular models. This work provided important insights into the physiopathology of HSP, and in particular on the possible existence of a developmental component to these adult-onset disorders. Since my recruitment as a CR2 INSERM (2012), I have developed a small research group in J. Hazan’s team. Over the last past years, my group as pioneered the use of multi-system approaches – including in vivo live imaging of cellular processes in navigating axons – to explore the role of microtubule-destabilizing proteins – involved in neurological disorders – in the wiring of neuronal circuits. Our work provided key molecular insights into the basic mechanisms underlying neuronal connectivity in healthy and pathological conditions. In 2019, I moved to the Institut de la Vision where I have established my group in X. Nicol’s team. Here, I develop fundamental/translational projects aiming at (i) identifying the guidance signalling pathways that regulates cytoskeleton remodelling in navigating axons, (ii) assessing the role of these guidance pathways in microtubule-related disorders as well as (iii) their relevance as potential actionable therapeutic targets to prevent axonal degeneration or promote directed axon (re)growth. In 2023, I became the co-lead of the team “Sensory and Motor Circuit Development” with Xavier Nicol at the Vision Institute.
Major publications:
1- Bécret J, Michaud C, Assali A, Chenais NAL, Kankadze I, Gomez-Bravo C, Roche F, Couvet S, Fassier C, and Nicol X. (2025). Point contact-restricted cAMP signaling control ephrin-A5-induced axon repulsion. J Cell Sci. 8: jcs.263480.
2- Ten Martin D, Jardin N, Vougny J, Giudicelli F, Gasmi L, Henriot H, Lebrun L, Haumaître C, Kneussel M, Nicol X, Janke C, Magiera M, Hazan J* and Fassier C*. (2024). Tubulin polyglutamylation patterns are central to axon guidance via selective regulation of microtubule-severing enzymes. EMBO J. Nov 29. (*equal contribution).
3- Bonnet M, Roche F, Fagotto-Kaufmann C, Gazdagh G, Truong I, Comunale F, Barbosa S, Bonhomme M, Nafati N, Hunt D, Pons Rodriguez M, Chaudhry A, Shears D, Madruga M, Vansenne F, Curie A, Kajava A.V, Baralle D, Fassier C, Debant A* and Schmidt S* (2023). Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo. Mol Psychiatry. 28:1527-1544. (* equal contribution).
4- Atkins M, Nicol X, Fassier C (2023). Microtubule remodelling as a driving force of axon guidance and pruning. Semin Cell Dev Biol.140:35-53.
5- Atkins M, Hazan J and Fassier C. (2022). In vivo live imaging of axonal transport in developing zebrafish axons. Methods Mol Biol. 2431:325-350.
6- Atkins M, Gasmi L, Bercier V, Revenu C, Del Bene F, Hazan J and Fassier C. (2019). Fignl1 associates with kif1bβ and bicd1 to restrict dynein transport velocity during axon navigation. J Cell Biol. 218:3290-3306.
7- Jardin N, Giudicelli F, Ten Martín D, De Gois R, Allison R, Houart C, Reid E, Hazan J and Fassier C. (2018). Bmp- and neuropilin-1-mediated motor axon navigation relies on spastin alternative translation. Development. 145(17).
8- Fassier C, Fréal A, Gasmi L, Delphin C, Ten Martin D, De Gois S, Tambalo M, Bosc C, Mailly P, Revenu C, Peris L, Bolte S, Schneider-Maunoury S, Houart C, Nothias F, Larcher JC, Andrieux A, Hazan J. (2018). Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics. J Cell Biol. 217:1719-1738.
9- Fassier C, Tarrade A, Peris L, Courageot S, Mailly P, Dalard C, Delga S, Roblot N, Lefèvre J, Job D, Hazan J, Curmi PA, Melki J (2013) Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech. 6:72-83
10- Fassier C, Hutt JA, Scholpp S, Lumsden A, Giros B, Nothias F, Schneider-Maunoury S, Houart C, Hazan J (2010) Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway. Nat Neurosci. 13:1380-7.
11- Tarrade A*, Fassier C*, Courageot S, Charvin D, Vitte J, Peris L, Thorel A, Mouisel E, Fonknechten N, Roblot N, Seilhean D, Diérich A, Hauw JJ, Melki J (2006) A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet. 15:3544-55. (* equal contribution).