Automatic Segmentation of Drosophila Neural Compartments Using GAL4 Expression Data Reveals Novel Visual Pathways

Identifying distinct anatomical structures within the brain and developing genetic tools to target them are fundamental steps for understanding brain function. We hypothesize that enhancer expression patterns can be used to automatically identify functional units such as neuropils and fiber tracts. We used two recent, genome-scale Drosophila GAL4 libraries and associated confocal image datasets to segment large brain regions into smaller subvolumes. Our results (available at https://strawlab.org/braincode) support this hypothesis because regions with well-known anatomy, namely the antennal lobes and central complex, were automatically segmented into familiar compartments. The basis for the structural assignment is clustering of voxels based on patterns of enhancer expression. These initial clusters are agglomerated to make hierarchical predictions of structure. We applied the algorithm to central brain regions receiving input from the optic lobes. Based on the automated segmentation and manual validation, we can identify and provide promising driver lines for 11 previously identified and 14 novel types of visual projection neurons and their associated optic glomeruli. The same strategy can be used in other brain regions and likely other species, including vertebrates. [Display omitted] •Genome-scale enhancer expression patterns can be used to predict brain structure•Automated clustering of images finds known structures such as olfactory glomeruli•Results identify GAL4 lines with strong expression in the predicted structures•We validate novel predictions to reveal previously undescribed optic glomeruli In this study, Panser et al. took advantage of recent, genome-wide Drosophila enhancer expression datasets consisting of 3D brain image volumes and used clustering to automatically predict brain structures. They validated previously described regions and used novel predictions to make an atlas of the fly optic glomeruli.