The purpose of our research is to elucidate molecular mechanisms that regulate cell-cell communication during development. We focus on two related questions: 1) how are tissues patterned and correctly connected by long-range signals, and 2) how cells structures and functions are coordinated at short-range with those of their neighbors. BMPs modulate long-range signaling during patterning, but also ensure short-range communication at specialized cell-cell interaction zones, for example the neuromuscular junction (NMJ). Through studies on extracellular modulators of BMP signaling we aim to elucidate mechanisms that shape cell-cell communication during early patterning and at NMJ synapses.
In recent years we have initiated a groundbreaking project to understand the mechanisms of synapse assembly using the Drosophila NMJ as a genetic model. Drosophila NMJ is a glutamatergic synapse, similar in structure and physiology to mammalian central AMPA/Kainate synapses. In flies, each NMJ is unique and identifiable, synapses are large and accessible for electrophysiological and optical analysis, making the Drosophila NMJ a favorite genetic system to study synapse development. The subunits that form the glutamate-gated ion channels (iGluRs) are known and relatively well studied. However, the mechanisms that control iGluRs clustering and stabilization at postsynaptic densities remain a mystery. We have discovered a novel, essential protein, Neto (Neuropillin and Tolloid-like), that is absolutely required for iGluRs clustering at the Drosophila NMJ. Neto is the first auxiliary protein described in Drosophila and is the only non-channel subunit required for functional glutamate receptors. These findings provide an entry point to understand the molecular mechanisms of synapse development.
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