Proper synaptic development is critical for establishing all aspects of neural function including learning, memory, and locomotion. Here, we describe the phenotypic consequences of mutations in the wishful thinking (wit) gene, the Drosophila homolog of the vertebrate BMP type II receptor. Mutations in wit result in pharate lethality that can be rescued by expression of a wit transgene in motor neurons but not in muscles. Mutant larvae exhibit small synapses, severe defects in evoked junctional potentials, a lower frequency of spontaneous vesicle release, and an alteration in the ultrastructure of synaptic active zones. These results reveal a novel role for BMP signaling in regulating Drosophila neuromuscular junction synapse assembly and activity and may indicate that similar pathways could govern vertebrate synapse development.
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We thank Steve Harrison and Rob Jackson for generously supplying us with a large number of mutant alleles from the 64A region. We are also grateful to Hermann Aberle, Brian McCabe, Corey Goodman, Joel Rawson, and Scott Selleck, for communication of results prior to publication. We gratefully acknowledge Alberto Ferrús for advice during the early stages of this project and support in histological analysis and Hugo Bellen in whose lab the electrophysiological analysis was initiated. We thank Joumana Jamal for help in isolating a full-length wit cDNA. Gib Ahlstrand is gratefully acknowledged for training G.M. in EM techniques. We thank P. ten Dijke, C. Goodman, K. Zinsmaier, S. Thor, and P. Salvaterra for reagents. The monoclonal 2B8 developed by K. Zinn was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of NICHD and maintained at the University of Iowa, Department of Biological Siences, Iowa City, Iowa 52242. This work was supported by a fellowship from NATO to G.M. and a grant from March of Dimes to M.B.O.; B.Z. and H.B. were supported by UT start up funds and a CAREER award (IBN-0093170) from the NSF. M.B.O. is an Associate Investigator with the Howard Hughes Medical Institute.