A study conducted by the “Neuromuscular connectivity in health and pathologies” team led by Laure Strochlic and Bertrand Fontaine at the Institute’s Myology Centre for Research has just been published in Science Signaling*. This work demonstrates the existence of a new communication pathway in the neuromuscular junction that is active both during embryogenesis and at the adult stage. Interview with Laure Strochlic
What is the context of this project?
The neuromuscular junction (NMJ) is the contact zone established between motor neurons and the muscle fibres they innervate. This synapse is responsible for the initiation and control of movement. The development of the neuromuscular junction requires dynamic trans-synaptic coordination orchestrated by factors secreted by different components of the NMJ, including morphogens of the Wnt family (a protein that specifies different cell types or regions of an organism depending on its concentration and whose role is essential during embryonic development).
What was the purpose of the study and how did you go about it?
We investigated how these synaptic signals are transmitted during JNM development, in particular during the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane. To this end, we explored the function of the Vangl2 protein, a central component of Wnt planar cell polarity signalling.
What results did you achieve?
We found that conditional and muscle-specific ablation of Vangl2 in mice reproduces the defects in JNM differentiation observed in mice with a global deletion of Vangl2. We also noted that these alterations persist into adulthood and lead to disassembly of JNM, impaired neurotransmission and deficits in motor function.
What conclusions did you draw?
Our results identify Vangl2 as a key player in the central complex of molecules that shape neuromuscular synapses and thus shed light on the molecular mechanisms underlying JNM assembly during embryogenesis. They also highlight its role in maintaining the normal function of JNMs in the adult stage.
* Boëx M, Cottin S, Halliez M, Bauché S, Buon C, Sans N, Montcouquiol M, Molgó J, Amar M, Ferry A, Lemaitre M, Rouche A, Langui D, Baskaran A, Fontaine B, Messéant J, Strochlic L. The cell polarity protein Vangl2 in the muscle shapes the neuromuscular synapse by binding to and regulating the tyrosine kinase MuSK. Sci Signal. 2022 May 17;15(734):eabg4982. doi: 10.1126/scisignal.abg4982. Epub 2022 May 17. PMID: 35580169.