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First published online 14 September 2005
doi: 10.1242/dev.02044

Development 132, 4471-4481 (2005)
Published by The Company of Biologists 2005
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Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations

Heather Flanagan-Steet1,*, Michael A. Fox2,*, Dirk Meyer3 and Joshua R. Sanes1,2,{dagger}

1 Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, MO 63110, USA
2 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
3 Biology I, University of Freiburg, 79104 Freiburg, Germany

{dagger} Author for correspondence (e-mail: sanesj{at}mcb.harvard.edu)

Accepted 12 August 2005

Synapse formation requires the coordination of pre- and postsynaptic differentiation. An unresolved question is which steps in the process require interactions between pre- and postsynaptic cells, and which proceed cell-autonomously. One current model is that factors released from presynaptic axons organize postsynaptic differentiation directly beneath the nerve terminal. Here, we used neuromuscular junctions (NMJs) of the zebrafish primary motor system to test this model. Clusters of neurotransmitter (acetylcholine) receptors (AChRs) formed in the central region of the myotome, destined to be synapse-rich, before axons extended and even when axon extension was prevented. Time-lapse imaging revealed that pre-existing clusters on early-born slow (adaxial) muscle fibers were incorporated into NMJs as axons advanced. Axons were, however, required for the subsequent remodeling and selective stabilization of synaptic clusters that precisely appose post- to presynaptic elements. Thus, motor axons are dispensable for the initial stages of postsynaptic differentiation but are required for later stages. Moreover, many AChR clusters on later-born fast muscle fibers formed at sites that had already been contacted by axons, suggesting heterogeneity in the signaling mechanisms leading to synapse formation by a single axon.

Key words: Acetylcholine receptor, Muscle, Neuromuscular junction, Zebrafish




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