The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formation

Lin, S. and Landmann, L. and Ruegg, M. A. and Brenner, H. R.. (2008) The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formation. Journal of neuroscience, Vol. 28, H. 13. pp. 3333-3340.

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Official URL: http://edoc.unibas.ch/dok/A5258377

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Neuromuscular junctions (NMJs) normally form in the central region of developing muscle. In this process, agrin released from motor neurons has been considered to initiate the formation of synaptic acetylcholine receptor (AChR) clusters (neurocentric model). However, in muscle developing in the absence of nerves and thus of agrin, AChR clusters still form in the muscle center. This raises the possibility that the region of NMJ formation is determined by muscle-derived cues that spatially restrict the nerve to form synapses from aneural AChR clusters, e.g., by patterned expression of the agrin receptor MuSK (muscle-specific kinase) (myocentric model). Here we examine at initial stages of synaptogenesis whether the responsiveness of myotubes to agrin is spatially restricted, whether the regions of NMJ formation in wild-type muscle and of aneural AChR cluster formation in agrin-deficient animals correlate, and whether AChR cluster growth depends on the presence of agrin. We show that primary myotubes form AChR clusters in response to exogenous agrin in their central region only, a pattern that can spatially restrict NMJ formation. However, the nerve also makes synapses in regions in which aneural AChR clusters do not form, and agrin promotes synaptic cluster growth from the first stages of neuromuscular contact formation. These data indicate that aneural AChR clusters per se are not required for NMJ formation. A model is proposed that explains either the neurocentric or the myocentric mode of NMJ formation depending on a balance between the levels of MuSK expression and the availability of nerve-released agrin.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Molecular Neurobiology Synapse Formation (Brenner)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Brenner, Hans-Rudolf and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Dec 2015 10:42
Deposited On:22 Mar 2012 13:20

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