The formation of functional neuronal circuits during brain development requires tightly coordinated synaptogenesis – deficits during this stage can lead to autism. Synaptic vesicles fuse at presynaptic active zones (AZs), which are multi-protein ensembles of largely unknown composition, function and assembly. Our studies in Drosophila identified a master organizer of AZ assembly (Bruchpilot) and 80-nm dense core vesicles, which are both associated with the assembly of AZs and similar to putative AZ precursor vesicles from mice.
We plan to investigate AZ assembly by a combination of in vivo imaging, genetics and ultrastructural methods at both Drosophila neuromuscular and murine hippocampal synapses. Moreover, we intend to characterize mutations of active zones proteins from autism patients.
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