Whole-brain annotation and multi-connectome cell typing of Drosophila
The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome<sup>1</sup> with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome<sup>2</sup>, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics.
Authors
- Claire McKellar (ORCID: https://orcid.org/0000-0002-3580-7336)
- Eric Perlman (ORCID: https://orcid.org/0000-0001-5542-1302)
- Varun Aniruddha Sane (ORCID: https://orcid.org/0000-0002-1945-1499)
- Szi-chieh Yu (ORCID: https://orcid.org/0009-0001-9684-0156)
- Yijie Yin (ORCID: https://orcid.org/0000-0002-5026-2602)
- Laia Serratosa Capdevila (ORCID: https://orcid.org/0000-0001-9167-0285)
- Siqi Fang (ORCID: https://orcid.org/0000-0002-7979-5170)
- Philipp Schlegel (ORCID: https://orcid.org/0000-0002-5633-1314)
- Sven Dorkenwald (ORCID: https://orcid.org/0000-0003-2352-319X)
- Tomke Stürner
- Irene Salgarella (ORCID: https://orcid.org/0000-0003-3817-3321)
- Christopher R Dunne (ORCID: https://orcid.org/0009-0007-2173-3667)
- Marina Gkantia (ORCID: https://orcid.org/0000-0002-3142-6384)
- H. Sebastian Seung (ORCID: https://orcid.org/0000-0002-8591-6733)
- Sridhar R. Jagannathan (ORCID: https://orcid.org/0000-0002-2078-1145)
- Alexandre Javier (ORCID: https://orcid.org/0000-0002-7942-6068)
- Daniel Han (ORCID: https://orcid.org/0000-0002-9088-1651)
- Gregory S.X.E. Jefferis (ORCID: https://orcid.org/0000-0002-0587-9355)
- Davi D. Bock (ORCID: https://orcid.org/0000-0002-8218-7926)
- Imaan FM Tamimi (ORCID: https://orcid.org/0000-0003-3332-0118)
- Griffin Badalamente (ORCID: https://orcid.org/0000-0003-1028-7343)
- Amy Sterling (ORCID: https://orcid.org/0000-0002-4961-3954)
- Katharina Eichler (ORCID: https://orcid.org/0000-0002-7833-8621)
- Alexandra M. C. Fragniere
- Alexander Shakeel Bates (ORCID: https://orcid.org/0000-0002-1195-0445)
- Marta Costa (ORCID: https://orcid.org/0000-0001-5948-3092)
- Mala Murthy (ORCID: https://orcid.org/0000-0003-3063-3389)
- Tom Kazimiers (ORCID: https://orcid.org/0000-0002-1605-9475)
- Paul Brooks (ORCID: https://orcid.org/0000-0001-5998-6378)
- Markus William Pleijzier (ORCID: https://orcid.org/0000-0002-7297-4547)
- Eva J Munnelly (ORCID: https://orcid.org/0000-0001-9284-9463)
- Marcia dos Santos (ORCID: https://orcid.org/0000-0003-4529-8464)
- Ladann Kiassat
- Arie Matsliah
Institutions
- University of Vermont (US)
- Champalimaud Foundation (PT)
- West Virginia University (US)
- California Institute of Technology (US)
- Massachusetts Eye and Ear Infirmary (US)
- Centre National de la Recherche Scientifique (FR)
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- University of Bonn (DE)
- Harvard University (US)
- Seoul National University (KR)
- Mount Holyoke College (US)
- Inserm (FR)
- University of California, Santa Barbara (US)
- University of California, Merced (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- University of California, Los Angeles (US)
- The University of Queensland (AU)
- MRC Laboratory of Molecular Biology (GB)
- Janelia Research Campus (US)
- Johannes Gutenberg University Mainz (DE)
- Princeton University (US)
- Université Côte d'Azur (FR)
- Cornell University (US)
- University of Cambridge (GB)
- University of Würzburg (DE)
- University of Mindanao (PH)
- Aware Global Hospital (IN)
- The Francis Crick Institute (GB)
- UNSW Sydney (AU)
- Yale University (US)
- National Dong Hwa University (TW)
- University of Florida (US)
- Gwangju Institute of Science and Technology (KR)
- University of Oxford (GB)
- Gliknik (United States) (US)
- Wellcome Centre for Integrative Neuroimaging (GB)
- Max Planck Florida Institute for Neuroscience (US)
- Hualien Tzu Chi Medical Center (TW)
- Health Awareness (United States) (US)
- Büchi Labortechnik (CH)
- Maqsut Narikbayev University (KZ)
- Max Planck Institute for Intelligent Systems (DE)
- Allen Institute (US)
- IIT@Harvard (US)
- Oldham Council (GB)
- Massachusetts Institute of Technology (US)
- Drexel University (US)
- Freie Universität Berlin (DE)
- Columbia University (US)
- Rockefeller University (US)
- Sungkyunkwan University (KR)
- Newcastle University (GB)
- RWTH Aachen University (DE)
- University of Haifa (IL)
- Leipzig University (DE)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- Nature
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1038/s41586-024-07686-5
- Citations
- 324
- Primary Topic
- Neurobiology and Insect Physiology Research
- Type
- article
- Field-Weighted Citation Impact
- 84.77