Derailed Regulates Development of the Drosophila Neuromuscular Junction

ABSTRACT: Neural function is dependent upon the proper formation and development of synapses. We show here that Wnt5 regulates the growth of the Drosophila neuromuscular junction (NMJ) by signaling through the Derailed receptor. Mutations in both wnt5 and drl result in a significant reduction in the number of synaptic bou-tons. Cell-type specific rescue experiments show that wnt5 functions in the presynaptic motor neuron while drl likely functions in the postsynaptic muscle cell. Epistatic analy-ses indicate that drl acts downstream of wnt5 to promote synaptic growth. Structure–function analyses of the Drl protein indicate that normal synaptic growth requires the extracellular Wnt inhibitory factor domain and the intra-cellular domain, which includes an atypical kinase. Our findings reveal a novel signaling mechanism that regu-lates morphology of the Drosophila NMJ. ' 2007 Wile