Wnt4 participates in the formation of vertebrate neuromuscular junction.

Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification of the early, spatially restricted cues in target recognition at the NMJ is still poorly documented, especially...

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Autores principales:	Laure Strochlic, Julien Falk, Evelyne Goillot, Séverine Sigoillot, Francine Bourgeois, Perrine Delers, Jérôme Rouvière, Amanda Swain, Valérie Castellani, Laurent Schaeffer, Claire Legay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df0d26cd828e4635976e9fa2cd27a89e
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spelling	oai:doaj.org-article:df0d26cd828e4635976e9fa2cd27a89e2021-11-18T07:30:21ZWnt4 participates in the formation of vertebrate neuromuscular junction.1932-620310.1371/journal.pone.0029976https://doaj.org/article/df0d26cd828e4635976e9fa2cd27a89e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253844/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification of the early, spatially restricted cues in target recognition at the NMJ is still poorly documented, especially in mammals. Wnt signaling is one of the key pathways regulating synaptic connectivity. Here, we report that Wnt4 contributes to the formation of vertebrate NMJ in vivo. Results from a microarray screen and quantitative RT-PCR demonstrate that Wnt4 expression is regulated during muscle cell differentiation in vitro and muscle development in vivo, being highly expressed when the first synaptic contacts are formed and subsequently downregulated. Analysis of the mouse Wnt4⁻/⁻ NMJ phenotype reveals profound innervation defects including motor axons overgrowing and bypassing AChR aggregates with 30% of AChR clusters being unapposed by nerve terminals. In addition, loss of Wnt4 function results in a 35% decrease of the number of prepatterned AChR clusters while Wnt4 overexpression in cultured myotubes increases the number of AChR clusters demonstrating that Wnt4 directly affects postsynaptic differentiation. In contrast, muscle structure and the localization of several synaptic proteins including acetylcholinesterase, MuSK and rapsyn are not perturbed in the Wnt4 mutant. Finally, we identify MuSK as a Wnt4 receptor. Wnt4 not only interacts with MuSK ectodomain but also mediates MuSK activation. Taken together our data reveal a new role for Wnt4 in mammalian NMJ formation that could be mediated by MuSK, a key receptor in synaptogenesis.Laure StrochlicJulien FalkEvelyne GoillotSéverine SigoillotFrancine BourgeoisPerrine DelersJérôme RouvièreAmanda SwainValérie CastellaniLaurent SchaefferClaire LegayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29976 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laure Strochlic Julien Falk Evelyne Goillot Séverine Sigoillot Francine Bourgeois Perrine Delers Jérôme Rouvière Amanda Swain Valérie Castellani Laurent Schaeffer Claire Legay Wnt4 participates in the formation of vertebrate neuromuscular junction.
description	Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification of the early, spatially restricted cues in target recognition at the NMJ is still poorly documented, especially in mammals. Wnt signaling is one of the key pathways regulating synaptic connectivity. Here, we report that Wnt4 contributes to the formation of vertebrate NMJ in vivo. Results from a microarray screen and quantitative RT-PCR demonstrate that Wnt4 expression is regulated during muscle cell differentiation in vitro and muscle development in vivo, being highly expressed when the first synaptic contacts are formed and subsequently downregulated. Analysis of the mouse Wnt4⁻/⁻ NMJ phenotype reveals profound innervation defects including motor axons overgrowing and bypassing AChR aggregates with 30% of AChR clusters being unapposed by nerve terminals. In addition, loss of Wnt4 function results in a 35% decrease of the number of prepatterned AChR clusters while Wnt4 overexpression in cultured myotubes increases the number of AChR clusters demonstrating that Wnt4 directly affects postsynaptic differentiation. In contrast, muscle structure and the localization of several synaptic proteins including acetylcholinesterase, MuSK and rapsyn are not perturbed in the Wnt4 mutant. Finally, we identify MuSK as a Wnt4 receptor. Wnt4 not only interacts with MuSK ectodomain but also mediates MuSK activation. Taken together our data reveal a new role for Wnt4 in mammalian NMJ formation that could be mediated by MuSK, a key receptor in synaptogenesis.
format	article
author	Laure Strochlic Julien Falk Evelyne Goillot Séverine Sigoillot Francine Bourgeois Perrine Delers Jérôme Rouvière Amanda Swain Valérie Castellani Laurent Schaeffer Claire Legay
author_facet	Laure Strochlic Julien Falk Evelyne Goillot Séverine Sigoillot Francine Bourgeois Perrine Delers Jérôme Rouvière Amanda Swain Valérie Castellani Laurent Schaeffer Claire Legay
author_sort	Laure Strochlic
title	Wnt4 participates in the formation of vertebrate neuromuscular junction.
title_short	Wnt4 participates in the formation of vertebrate neuromuscular junction.
title_full	Wnt4 participates in the formation of vertebrate neuromuscular junction.
title_fullStr	Wnt4 participates in the formation of vertebrate neuromuscular junction.
title_full_unstemmed	Wnt4 participates in the formation of vertebrate neuromuscular junction.
title_sort	wnt4 participates in the formation of vertebrate neuromuscular junction.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/df0d26cd828e4635976e9fa2cd27a89e
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Wnt4 participates in the formation of vertebrate neuromuscular junction.

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