QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 26, 2008, 28(13):3333-3340; doi:10.1523/JNEUROSCI.5590-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Lin, S. Articles by Brenner, H. R. Search for Related Content PubMed PubMed Citation Articles by Lin, S. Articles by Brenner, H. R.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Role of Nerve- versus Muscle-Derived Factors in Mammalian Neuromuscular Junction Formation

Shuo Lin,¹ Lukas Landmann,² Markus A. Ruegg,¹ and Hans Rudolf Brenner³

¹Biozentrum and Institutes of ²Anatomy and ³Physiology, Department of Biomedicine, University of Basel, CH-4056 Basel, Switzerland

Correspondence should be addressed to Hans Rudolf Brenner, Institute of Physiology, Department of Biomedicine, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Email: hans-rudolf.brenner{at}unibas.ch

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.

Key words: agrin; MuSK; synapse formation; development; neuromuscular junction; muscle

---

Received Dec. 18, 2007; revised Feb. 11, 2008; accepted Feb. 13, 2008.

Correspondence should be addressed to Hans Rudolf Brenner, Institute of Physiology, Department of Biomedicine, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Email: hans-rudolf.brenner{at}unibas.ch

This article has been cited by other articles:

				R. Ramseger, R. White, and S. Kroger Transmembrane Form Agrin-induced Process Formation Requires Lipid Rafts and the Activation of Fyn and MAPK J. Biol. Chem., March 20, 2009; 284(12): 7697 - 7705. [Abstract] [Full Text] [PDF]

				J. P. Henriquez, A. Webb, M. Bence, H. Bildsoe, M. Sahores, S. M. Hughes, and P. C. Salinas Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin PNAS, December 2, 2008; 105(48): 18812 - 18817. [Abstract] [Full Text] [PDF]

				F. Chevessier, E. Girard, J. Molgo, S. Bartling, J. Koenig, D. Hantai, and V. Witzemann A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions Hum. Mol. Genet., November 15, 2008; 17(22): 3577 - 3595. [Abstract] [Full Text] [PDF]

				H. Nishimune, G. Valdez, G. Jarad, C. L. Moulson, U. Muller, J. H. Miner, and J. R. Sanes Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction J. Cell Biol., September 22, 2008; 182(6): 1201 - 1215. [Abstract] [Full Text] [PDF]

				S. Lin, M. Maj, G. Bezakova, J. P. Magyar, H. R. Brenner, and M. A. Ruegg Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice PNAS, August 12, 2008; 105(32): 11406 - 11411. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help