SPATIOTEMPORAL ASSEMBLY OF PARALLEL VISUAL PATHWAYS IN <EM >DROSOPHILA</EM>

Distinct visual cues are computed by specific neural circuits whose assembly relies on bidirectional interactions between specific neuron types during development. Nevertheless, the cellular and subcellular dynamics governing partner selection between pre- and postsynaptic neurons remain poorly understood. We address this question using the functionally specialized dorsal rim area (DRA) of the Drosophila visual system, which forms a modality-specific circuit for processing skylight polarization while avoiding synaptic connections with nearby color-sensitive neurons.
We focus on the developmental assembly of UV-sensitive photoreceptors and their polarization- versus color-sensitive postsynaptic targets, the MeTu visual projection neurons. Using quantitative ex vivo time-lapse imaging, we characterize dynamic cellular interactions during development and utilize connectomic analyses to identify adult ‘footprints’ of developmental processes. Our results show that directed neurite growth increases the likelihood of correct partner matching, whereas inappropriate synaptic connections are prevented through spatiotemporal separation. In parallel, developmental single-cell RNA sequencing reveals candidate molecular mechanisms that may bias or stabilize exploratory filopodial interactions. We identify the homophilic cell adhesion molecule Connectin as being selectively expressed in both pre- and postsynaptic neurons of the developing DRA circuit. Differential Connectin expression in MeTus regulates extension of their dendritic filipodia, leading to modality-specific connectivity. We therefore propose that intrinsic synaptic promiscuity can be harnessed by regulating specific spatiotemporal adjacencies.
Together, our findings support a functionally testable developmental mechanism in which modality-specific circuits emerge through spatiotemporal restriction of neuron–neuron interactions and adjacency, enabling the assembly of parallel processing pathways of closely related neuron types.