Neuromuscular Connectivity in health and diseases

Our laboratory aims to understand the cellular and molecular mechanisms underlying neuromuscular synapse assembly and maintenance in physiological and pathological conditions.

The Neuromuscular junction (NMJ) is the contact zone between motor neurons and skeletal muscles. This synapse drives the precise initiation and control of motion. Therefore, much of our behavior and wellness relies on the appropriate functioning of this specialised structure. Neuromuscular transmission deficiency occurs in a large array of rare human diseases including channelopathies, congenital or acquired myasthenia and amyotrophic lateral sclerosis. Most of these pathologies are untreatable and life threatening with devastating economic and societal consequences in terms of loss of quality of life and of the burden of disability. The patients display complex clinical phenotypes mainly characterized by a profound muscle weakness and loss of mobility.

We combine unbiased screens and a large array of functional assays including quantitative morphological imaging, behavioral analysis and electrophysiology using mouse models and/or human-derived specimens to explore the complexity of the trans-synaptic mechanisms controlling neuromuscular connectivity. Our overarching goal is to improve physiopathological knowledge that can be used not only for molecular diagnosis and genetic counselling of families affected with the diseases of interest, but also to design new targets of therapeutic interest.

To achieve this goal, our team is built on an organization that favors tight interactions between practicing neurologists from the Paris Est French reference center for neuromuscular diseases and researchers/research assistants together with a large network of national/international collaborations to share knowledge and expertise.

Team 10

We defined three main aims of research:

1) Characterize the molecular determinants underlying NMJ assembly and maintenance (PI: Laure Strochlic/Julien Messéant).

We have recently identified a new trans-synaptic pathway at the NMJ and developed innovative tools using mouse genetics to dissect its molecular characteristics.

2) Understand how disruption of nerve/muscle communication leads to neuromuscular diseases such as myasthenia and amyotrophic lateral sclerosis (PI: Stéphanie Godard-Bauché/Gaelle Bruneteau).

Thanks to our clinical expertise and our national networks, we analyze the physiopathological mechanisms underlying the studied diseases in patients.

3) Modulate trans-synaptic function to restore appropriate synaptic connectivity in a pathological context as a basis for therapeutic interventions (PI: Bertrand Fontaine/Laure Strochlic).

We develop innovative pharmacological or genetic strategies that promote trans-synaptic communication and nerve/muscle attachment to mitigate NMJ disease symptoms to ultimately prevent or compensate the progression of the loss of motor function in neuromuscular diseases.

Key words: Neuromuscular Junction, Neuromuscular disorders, disease modeling mouse models, human derived specimens, quantitative imaging, therapeutic strategies.

Main collaborations:

  • Rozen Le Panse and Sonia Berrih-Aknin (France)
  • Arnaud Ferry (France)
  • Cécile Martinat (France)
  • Eric Krejci (France)
  • Frédérique Charbonnier (France)
  • Nathalie Sans and Mireille Montcouquiol (France)
  • Laurent Schaeffer, NeuroMyoGene Institute, (France)
  • Hanns Lochmüller, The Children’s Hospital of Eastern Ontario (Canada)
  • Markus Ruëgg, Biozentrum (Switzerland)
  • Anna Punga, Uppsala University, (Sweden)





105 documents

  • A. Corvó, L. Matalonga, C. Hernandez-Ferrer, R. Thompson, L. Carmody, et al.. Treatabolome DB: linking gene and variants with treatments for rare diseases. Solve-RD, Solving the unsolved Rare Diseases Final Meeting 2023, Apr 2023, Prague, Czech Republic. ⟨hal-04086225⟩
  • Marius Halliez. Le domaine riche en cystéine de MuSK dans la myasthénie auto-immune. Biologie cellulaire. Sorbonne Université, 2023. Français. ⟨NNT : 2023SORUS093⟩. ⟨tel-04137804⟩
  • Marion Masingue, Olivia Cattaneo, Nicolas Wolff, Céline Buon, Damien Sternberg, et al.. New mutation in the β1 propeller domain of LRP4 responsible for congenital myasthenic syndrome associated with Cenani–Lenz syndrome. Scientific Reports, 2023, 13 (1), pp.14054. ⟨10.1038/s41598-023-41008-5⟩. ⟨hal-04191765⟩
  • Tanya Stojkovic, Marion Masingue, Helène Turmel, Marianne Hezode-Arzel, Anthony Béhin, et al.. Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes. Neuromuscular Disorders, 2022, 32 (11-12), pp.870-878. ⟨10.1016/j.nmd.2022.10.001⟩. ⟨hal-04074000⟩
  • Stéphanie Bauché, Marion Masingue, Olivia Cattaneo, Damien Sternberg, Céline Buon, et al.. New mutation in the beta 1 propeller domain of LRP4 responsible for congenital myasthenic syndrome associated with Cenani-Lenz syndrome. journées de la société française de myologie, Nov 2022, Toulouse, France. ⟨hal-03994163⟩
  • Sestina Falcone, Marais T., Traoré M., Bourguiba A., Gentil C., et al.. Unraveling the role of GDF5 therapeutic potential in Amyotrophic Lateral Sclerosis. 19 Journée de la societé Française de Myologie, Nov 2022, Toulouse (FR), France. ⟨hal-04002173⟩
  • Arnaud Jacquier, Valérie Risson, Thomas Simonet, Florine Roussange, Nicolas Lacoste, et al.. Severe congenital myasthenic syndromes caused by agrin mutations affecting secretion by motoneurons. Acta Neuropathologica, 2022, 144 (4), pp.707-731. ⟨10.1007/s00401-022-02475-8⟩. ⟨hal-03863096⟩
  • Charles Frison-Roche, Steve Cottin, Jeanne Lainé, Ludovic Arandel, Marius Halliez, et al.. MBNL loss of function in motoneurons leads to motor unit dysfunction in myotonic dystrophy. 7th International Myology Congress, Sep 2022, Nice, France. ⟨hal-04005838⟩
  • Sestina Falcone, T. Marais, M. Traoré, C. Gentil, J. Mésseant, et al.. Unraveling the role of GDF5 therapeutic potential in Amyotrophic Lateral Sclerosis. Myology 2022, Sep 2022, Nice (FRANCE), France. ⟨hal-04002164⟩
  • laure strochlic. Entre muscle et nerf: comprendre la jonction neuromusculaire pour mieux comprendre le mouvement. The Conversation France, 2022. ⟨inserm-03774979⟩
Assistance Publique Hôpitaux de Paris
Fondation de l'avenir - Accélérateur de progrès médical
Association pour la recherche sur la SLA
Satt Lutech
Inserm Transfert
AMO Pharma

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