The role of Wnt proteins in neuromuscular junction formation

Research Published April 27 2017
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2727The neuromuscular junction is the area that enables transfer of information from the nervous system to muscles. It is composed of a motor neuron that transfers information to a muscle thanks to a neurotransmitter called acetylcholine. The contact zone between the two creates a synapse, with a presynaptic neuron and a postsynaptic muscle.

Understanding how this junction is formed is essential given that dysfunction is involved in many pathologies including myasthenia.

An increasing number of studies suggest that a family of proteins called Wnts may play a key role in neuromuscular junction formation in several vertebrate species. Functions and molecular mechanisms they are involved in, however, remain unclear.

Laure Strochlic from the team led by Bertrand Fontaine and collaborators used experimental modelling to test the role of different Wnt proteins in neuromuscular junction formation and signaling cascades, meaning the sequence of events within cells they act upon.

Results show that Wnt4 and Wnt11 proteins play a key role in neuromuscular junction formation. They regulate axon growth (neuron extension that conducts the electric signal) in motor neurons and, additionally, they activate acetylcholine receptor grouping in muscles. Researchers also found that the action of these proteins is mediated by two different Wnt signaling pathways that are essential in development: the “β-catenin” pathway and the PCP pathway (Planar Cell Polarity).

As a whole, these results shed new light on a mechanism that enables neuromuscular junction implementation. This data opens up new perspectives in treatment of illnesses that affect neuromuscular transmission including myasthenia using Wnt pathway-modulating pharmacological molecules.

Source: Wnts contribute to neuromuscular junction formation through distinct signaling pathways. Messéant J, Ezan J, Delers P, Glebov K, Marchiol C, Lager F, Renault G, Tissir F, Montcouquiol M, Sans N, Legay C, Strochlic L. Development. 2017 Mar 27.

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Gene therapy Main domain: Clinical & translational neurosciences Subdomain : Molecular & cellular neuroscience Nathalie CARTIER’s team develops gene therapy strategies for severe neurodegenerative diseases including Huntington's disease, Spinocerebellar ataxias, Alzheimer's disease and genetic leukodystrophies. Research includes proof of concept in animal models and translational steps to clinical applications. The team aims to propose a phase I/II therapeutic trial in 2020 for Huntington disease. The team will also develop tools for the delivery of therapeutic molecules in the brain (use of microglia, optimization of AAV for intravenous administration, optogenerapy for time-controlled delivery).
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