BMP signaling is required for synapse assembly at the Drosophila neuromuscular junction. Mikolaj J Sulkowski1, Young-Jun Kim1, Bing Zhang2, Mihaela Serpe1. 1) Program in Cellular Regulation and Metabolism, NICHD, NIH, Bethesda, MD, USA, 20892; 2) Department of Zoology, University of Oklahoma, Norman, OK, USA, 73019.
Formation of neural circuits begins with physical assembly of the synapses and stabilization of postsynaptic densities, followed by synapse maturation and growth, and finally elimination of synapses during development. The coordinated growth of synaptic structures requires communication between the pre- and postsynaptic compartments and relies on anterograde and retrograde signals, and on the activity of the neural circuit itself. Drosophila NMJ is a glutamatergic synapse similar in composition and physiology to our central synapses. We have recently discovered that the neto gene is absolutely required for the initial clustering of glutamate receptors (iGluRs) at the Drosophila NMJ. neto null mutant embryos are completely paralyzed and lack iGluRs clusters at their NMJs. neto hypomorphs have diminished levels of synaptic receptors, and have smaller synapses with reduced quantal size, and no compensatory increase in quantal content. The reduced synapse growth and lack of presynaptic compensation are reminiscent of defects in the BMP retrograde signaling. At the Drosophila NMJ, Glass bottom boat (Gbb), a BMP-type ligand secreted by the muscle, provides a retrograde signal essential for coordinating the growth of synaptic structures. Retrograde BMP signaling induces phosphorylation of Mad (pMad) at synaptic terminals and in neuron nuclei. We found that at suboptimal Neto levels, pMad is completely absent from the NMJ, but it is not affected in the motor neuron nuclei. We will review our recent data that suggest that BMP signaling is required for synapse assembly at the Drosophila NMJ.