Whole-brain annotation and multi-connectome cell typing of Drosophila
Authors: Schlegel Philipp , Yin Yijie , Bates Alexander S. , Dorkenwald Sven , Eichler Katharina , Brooks Paul , Han Daniel S. , Gkantia Marina , dos Santos Marcia , Munnelly Eva J. , Badalamente Griffin , Serratosa Capdevila Laia , Sane Varun A. , Fragniere Alexandra M. C. , Kiassat Ladann , Pleijzier Markus W. , Stürner Tomke , Tamimi Imaan F. M. , Dunne Christopher R. , Salgarella Irene , Javier Alexandre , Fang Siqi , Perlman Eric , Kazimiers Tom , Jagannathan Sridhar R. , Matsliah Arie , Sterling Amy R. , Yu Szi-chieh , McKellar Claire E. ,   FlyWire Consortium, Kruk Krzysztof , Bland Doug , Lenizo Zairene , Burke Austin T. , Willie Kyle Patrick , Bates Alexander S. , Serafetinidis Nikitas , Hadjerol Nashra , Willie Ryan , Silverman Ben , Ocho John Anthony , Bañez Joshua , Candilada Rey Adrian , Gager Jay , Kristiansen Anne , Panes Nelsie , Yadav Arti , Tancontian Remer , Serona Shirleyjoy , Dolorosa Jet Ivan , Vinson Kendrick Joules , Garner Dustin , Salem Regine , Dagohoy Ariel , Skelton Jaime , Lopez Mendell , Stocks Thomas , Pandey Anjali , Akiatan Darrel Jay , Hebditch James , David Celia , Sapkal Dharini , Monungolh Shaina Mae , Sane Varun , Pielago Mark Lloyd , Albero Miguel , Laude Jacquilyn , dos Santos Márcia , Deutsch David , Vohra Zeba , Wang Kaiyu , Gogo Allien Mae , Kind Emil , Mandahay Alvin Josh , Martinez Chereb , Asis John David , Nair Chitra , Patel Dhwani , Manaytay Marchan , Lim Clyde Angelo , Ampo Philip Lenard , Pantujan Michelle Darapan , Bautista Daril , Rana Rashmita , Seguido Jansen , Parmar Bhargavi , Saguimpa John Clyde , Moore Merlin , Pleijzier Markus W. , Larson Mark , Hsu Joseph , Joshi Itisha , Kakadiya Dhara , Braun Amalia , Pilapil Cathy , Parmar Kaushik , Vanderbeck Quinn , Dunne Christopher , Munnelly Eva , Kang Chan Hyuk , Lörsch Lena , Lee Jinmook , Kmecova Lucia , Sancer Gizem , Baker Christa , Joroff Jenna , Calle Steven , Patel Yashvi , Sato Olivia , Salocot Janice , Salman Farzaan , Molina-Obando Sebastian , Bui Mai , Lichtenberger Matthew , Tamboboy Edmark , Molloy Katie , Santana-Cruz Alexis E. , Hernandez Anthony , Yu Seongbong , Sorek Marissa , Diwan Arzoo , Patel Monika , Aiken Travis R. , Morejohn Sarah , Koskela Sanna , Yang Tansy , Lehmann Daniel , Chojetzki Jonas , Sisodiya Sangeeta , Koolman Selden , Shiu Philip K. , Cho Sky , Bast Annika , Reicher Brian , Blanquart Marlon , Houghton Lucy , Choi Hyungjun , Ioannidou Maria , Collie Matt , Eckhardt Joanna , Gorko Benjamin , Guo Li , Zheng Zhihao , Poh Alisa , Lin Marina , Taisz István , Murfin Wes , Díez Álvaro Sanz , Reinhard Nils , Gibb Peter , Patel Nidhi , Kumar Sandeep , Yun Minsik , Wang Megan , Jones Devon , Encarnacion-Rivera Lucas , Oswald Annalena , Jadia Akanksha , Erginkaya Mert , Drummond Nik , Walter Leonie , Tastekin Ibrahim , Zhong Xin , Mabuchi Yuta , Figueroa Santiago Fernando J. , Verma Urja , Byrne Nick , Kunze Edda , Crahan Thomas , Margossian Ryan , Kim Haein , Georgiev Iliyan , Szorenyi Fabianna , Adachi Atsuko , Bargeron Benjamin , Stürner Tomke , Demarest Damian , Gür Burak , Becker Andrea N. , Turnbull Robert , Morren Ashley , Sandoval Andrea , Moreno-Sanchez Anthony , Pacheco Diego A. , Samara Eleni , Croke Haley , Thomson Alexander , Laughland Connor , Dutta Suchetana B. , de Antón Paula Guiomar Alarcón , Huang Binglin , Pujols Patricia , Haber Isabel , González-Segarra Amanda , Lin Albert , Choe Daniel T. , Lukyanova Veronika , Mancini Nino , Liu Zequan , Okubo Tatsuo , Flynn Miriam A. , Vitelli Gianna , Laturney Meghan , Li Feng , Cao Shuo , Manyari-Diaz Carolina , Yim Hyunsoo , Duc Le Anh , Maier Kate , Yu Seungyun , Nam Yeonju , Bąba Daniel , Abusaif Amanda , Francis Audrey , Gayk Jesse , Huntress Sommer S. , Barajas Raquel , Kim Mindy , Cui Xinyue , Sterling Amy R. , Sterne Gabriella R. , Li Anna , Park Keehyun , Dempsey Georgia , Mathew Alan , Kim Jinseong , Kim Taewan , Wu Guan-ting , Dhawan Serene , Brotas Margarida , Zhang Cheng-hao , Bailey Shanice , Del Toro Alexander , Lee Kisuk , Macrina Thomas , Schneider-Mizell Casey , Popovych Sergiy , Ogedengbe Oluwaseun , Yang Runzhe , Halageri Akhilesh , Silversmith Will , Gerhard Stephan , Champion Andrew , Eckstein Nils , Ih Dodam , Kemnitz Nico , Castro Manuel , Jia Zhen , Wu Jingpeng , Mitchell Eric , Nehoran Barak , Mu Shang , Bae J. Alexander , Lu Ran , Morey Ryan , Kuehner Kai , Brittain Derrick , Jordan Chris S. , Anderson David J. , Behnia Rudy , Bidaye Salil S. , Borst Alexander , Chiappe Eugenia , Collman Forrest , Colodner Kenneth J. , Dacks Andrew , Dickson Barry , Funke Jan , Garcia Denise , Hampel Stefanie , Hartenstein Volker , Hassan Bassem , Helfrich-Forster Charlotte , Huetteroth Wolf , Kim Jinseop , Kim Sung Soo , Kim Young-Joon , Kwon Jae Young , Lee Wei-Chung , Linneweber Gerit A. , Maimon Gaby , Mann Richard , Noselli Stéphane , Pankratz Michael , Prieto-Godino Lucia , Read Jenny , Reiser Michael , von Reyn Katie , Ribeiro Carlos , Scott Kristin , Seeds Andrew M. , Selcho Mareike , Silies Marion , Simpson Julie , Waddell Scott , Wernet Mathias F. , Wilson Rachel I. , Wolf Fred W. , Yao Zepeng , Yapici Nilay , Zandawala Meet , Costa Marta , Seung H. Sebastian , Murthy Mala , Hartenstein Volker , Bock Davi D. , Jefferis Gregory S. X. E. 
Published: October 2024

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 connectome1 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 connectome2, 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.