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.

Scientific teams

Team leader
Francoise PIGUET Researcher, PhD, ICM
NEUROGENCELL Main field : Clinical & translational neurosciences Secondary domain: Molecular & cellular neurosciences The "NEUROGENCELL" team develops gene and cell therapy strategies for severe neurodegenerative diseases of adults and children: Amyotrophic lateral sclerosis, Huntington's, Spinocerebellar ataxias, Parkinson's and Rett syndrome. As well as paediatric overload diseases: genetic leukodystrophies and mucopolysaccharidoses. This research includes proof of concepts in animal models and translational steps towards clinical applications. The "NEUROGENCELL" team is also developing tools for the entry of therapeutic molecules into the brain (vectors that can be administered by the venous route, optogenetics, use of microglia as a therapeutic vector, use of ultrasound to improve the passage of vectors across the blood-brain barrier).
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