@article{3fcb35d8dc7e4659987881ab72e38148,
title = "Molecular topography of an entire nervous system",
abstract = "We have produced gene expression profiles of all 302 neurons of the C. elegans nervous system that match the single-cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses distinct codes of ∼23 neuropeptide genes and ∼36 neuropeptide receptors, delineating a complex and expansive “wireless” signaling network. To demonstrate the utility of this comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression and (2) reveal adhesion proteins with potential roles in process placement and synaptic specificity. Our expression data are available at https://cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity, and function throughout the C. elegans nervous system.",
keywords = "C. elegans, cell adhesion molecules, connectome, gene regulatory motifs, neuron, neuropeptides, RNA-seq, single-cell",
author = "Taylor, {Seth R.} and Gabriel Santpere and Alexis Weinreb and Alec Barrett and Reilly, {Molly B.} and Chuan Xu and Erdem Varol and Panos Oikonomou and Lori Glenwinkel and Rebecca McWhirter and Abigail Poff and Manasa Basavaraju and Ibnul Rafi and Eviatar Yemini and Cook, {Steven J.} and Alexander Abrams and Berta Vidal and Cyril Cros and Saeed Tavazoie and Nenad Sestan and Marc Hammarlund and Oliver Hobert and Miller, {David M.}",
note = "Funding Information: We thank the CeNGEN Advisory Board for guidance, M. Zhen for ZM9592, and H. Sun for imaging neuropeptide reporters. O.H. is an Investigator with the Howard Hughes Medical Institute. FACS (Flow Cytometry Shared Resource, supported by Ingram Cancer Center [ P30 CA68485 ], DDRC [ DK058404 ]), scRNA-seq (VANTAGE, supported by CTSA [ 5UL1 RR024975-03 ], Ingram Cancer Center [ P30 CA68485 ], Vision Center [P30 EY08126], and NIH/NCRR [ G20 RR030956 ]), and confocal imaging (Cell Imaging Shared Resource [ NIH CA68485 , DL20593 , DK58404 , DK59637 , and EY08126 ]) were performed at Vanderbilt. Strains were provided by the CGC ( NIH P40 OD010440A ). G.S. was supported by “la Caixa” Foundation ( LCF/BQ/PI19/11690010 , ID 100010434) and by Ministerio de Ciencia e Innovaci{\'o}n, Spain ( PID2019-104700GA-I00 ). This work was funded by NIH ( R01NS100547 to M.H., O.H., D.M.M., and N.S. and R01 NS110391 to O.H.) and by Vanderbilt TIPs (to D.M.M.). Funding Information: We thank the CeNGEN Advisory Board for guidance, M. Zhen for ZM9592, and H. Sun for imaging neuropeptide reporters. O.H. is an Investigator with the Howard Hughes Medical Institute. FACS (Flow Cytometry Shared Resource, supported by Ingram Cancer Center [P30 CA68485], DDRC [DK058404]), scRNA-seq (VANTAGE, supported by CTSA [5UL1 RR024975-03], Ingram Cancer Center [P30 CA68485], Vision Center [P30 EY08126], and NIH/NCRR [G20 RR030956]), and confocal imaging (Cell Imaging Shared Resource [NIH CA68485, DL20593, DK58404, DK59637, and EY08126]) were performed at Vanderbilt. Strains were provided by the CGC (NIH P40 OD010440A). G.S. was supported by ?la Caixa? Foundation (LCF/BQ/PI19/11690010, ID 100010434) and by Ministerio de Ciencia e Innovaci?n, Spain (PID2019-104700GA-I00). This work was funded by NIH (R01NS100547 to M.H. O.H. D.M.M. and N.S. and R01 NS110391 to O.H.) and by Vanderbilt TIPs (to D.M.M.). M.H. O.H. N.S. and D.M.M. originated project. S.R.T. generated scRNA-seq data; assigned neuron identities; analyzed gene family expression; helped A.W. C.X. E.V. and P.O. with data analysis; designed figures and tables; wrote the first draft; and edited the final version. G.S. developed CengenApp. A.W. designed thresholding strategy with S.R.T. analyzed alternative splicing, and implemented meta data format. A.B. generated and analyzed bulk RNA sequence data. M.B.R. provided ground truth reporters. C.X. extended 3? UTRs for read mapping. E.V. correlated CAMs with neuron-specific synapses and strata and provided input on statistical and quantitative analysis. P.O. implemented FIRE analysis with S.T. L.G. provided BrainAtlas. R.M. and A.P. used FACS to isolate neurons. R.M. extracted RNA for bulk RNA-seq. I.R. E.Y. S.J.C. B.V. C.C. M.B. A.A. and S.R.T. generated reporter strains. E.Y. helped with NeuroPAL. N.S. directed G.S. and C.X. and edited the manuscript. M.H. directed G.S. A.W. A.B. M.B. and A.A.; contributed to the first draft; and edited the final version. O.H. directed M.B.R. L.G. I.R. E.Y. S.C. B.V. and C.C.; contributed to the first draft; and edited the final version. D.M.M. oversaw work; directed S.R.T. R.M. and A.P.; contributed to the first draft; and edited the final version. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "5",
doi = "10.1016/j.cell.2021.06.023",
language = "English (US)",
volume = "184",
pages = "4329--4347.e23",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "16",
}