/ PROJECTS / RP7

We are interested in how individual neurons develop and maintain synaptic networks. Our approach is to observe how they do it with advanced live imaging in the intact fly brain.

The role of autophagy in synapse formation.
Local autophagy controls synapse formation through the regulation of filopodia lifetime in flies, as shown in Kiral et al., Nature Comm, 2020. The substrates of local synaptoc autophagy are largely unknown.Autophagy serves distinct local functions at developing and adult synaptic terminals. These functions rely on what substrates are engulfed and degraded in a time- and location-dependent manner, yet little is known about the substrate specificity of developmental autophagy versusautophagy at functional synapses. In RP7 we will investigate locally regulated autophagy at synaptic terminals compared to other cellular compartments in developing and adult neurons using photoreceptor neurons in the Drosophila brain as a model. This project is motivated by our recent discovery in these neurons that autophagosomes form selectively at the tips of synaptogenic filopodia during late brain development, thereby regulating synapse formation. What substrates underlie this process remains unknown. The identification of selective autophagy in the small space of a filopodial tip led us to hypothesize that the time and location of autophagosome formation may significantly restrict available substrates. This hypothesis provides an opportunity to test the general importance of restricted local substrate availability for spatiotemporally distinct roles of autophagy. We have therefore devised a substrate probe panel for comparative live imaging of local autophagy in collaboration with the entire Syntophagy consortium. Our first goal is to elucidate the mechanism of local autophagy during synapse formation. In addition, we strive to establish a first comparative, substrate-focused picture of spatiotemporally distinct roles of autophagy in developing and functional neurons