Autophagic regulation of synapse formation in the Drosophila brain
P. ROBIN HIESINGER (Freie Universität, Berlin)
In addition to its well-established role in neuronal maintenance, autophagy has been shown to fine-tune synapse development in the brains of mice, flies and worms. These roles of autophagy likely encompass many different, local mechanisms and cargoes. In RP7, we test the hypothesis that autophagy is multitude, with highly context-specific roles depending on when and where autophagosome biogenesis is triggered during brain development using Drosophila (fruit flies) as a model system. Specifically, we ask the question: Does the local utilization of autophagy necessarily differ in the context of different neurons, or are there shared roles and substrates across neuron types? To answer this question, we have chosen three interneuron types in the Drosophila brain to characterize shared and divergent roles of local autophagy during synapse formation in the brain. Our approaches are devised to learn more about local, context-specific cell-autonomous (Objective 1) and non-autonomous (Objective 2) roles of autophagy during synapse formation.
(from reference ‘Hassan and Hiesinger, Autophagy, 2023’); figure legend therein:
Regulation of synapse formation through two different mechanisms in two neuron types in Drosophila. (A) In fly photoreceptor neurons, autophagosome formation is selectively triggered at the tips of synaptogenic filopodia to regulate synapse numbers and partnerships. (B) In fly dorsal cluster neurons, autophagy is actively suppressed to stabilize synapses and branch formation.
References:
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Kiral F.R., Linneweber G.A., Mathejczyk T.F., Georgiev S.V., Wernet M.F., Hassan B.A., von Kleist M., Hiesinger P.R. (2020). Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring, preprint at BioRxiv, Nature Communications, 12;11(1):1325.
