A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes

Summary: Motor neurons (MNs) constitute an ancient cell type targeted by multiple adult-onset diseases. It is therefore important to define the molecular makeup of adult MNs in animal models and extract organizing principles. Here, we generate a comprehensive molecular atlas of adult Caenorhabditis...

Full description

Bibliographic Details
Main Authors: Jayson J. Smith, Seth R. Taylor, Jacob A. Blum, Weidong Feng, Rebecca Collings, Aaron D. Gitler, David M. Miller, III, Paschalis Kratsios
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724001852
_version_ 1827338148368089088
author Jayson J. Smith
Seth R. Taylor
Jacob A. Blum
Weidong Feng
Rebecca Collings
Aaron D. Gitler
David M. Miller, III
Paschalis Kratsios
author_facet Jayson J. Smith
Seth R. Taylor
Jacob A. Blum
Weidong Feng
Rebecca Collings
Aaron D. Gitler
David M. Miller, III
Paschalis Kratsios
author_sort Jayson J. Smith
collection DOAJ
description Summary: Motor neurons (MNs) constitute an ancient cell type targeted by multiple adult-onset diseases. It is therefore important to define the molecular makeup of adult MNs in animal models and extract organizing principles. Here, we generate a comprehensive molecular atlas of adult Caenorhabditis elegans MNs and a searchable database. Single-cell RNA sequencing of 13,200 cells reveals that ventral nerve cord MNs cluster into 29 molecularly distinct subclasses. Extending C. elegans Neuronal Gene Expression Map and Network (CeNGEN) findings, all MN subclasses are delineated by distinct expression codes of either neuropeptide or transcription factor gene families. Strikingly, combinatorial codes of homeodomain transcription factor genes succinctly delineate adult MN diversity in both C. elegans and mice. Further, molecularly defined MN subclasses in C. elegans display distinct patterns of connectivity. Hence, our study couples the connectivity map of the C. elegans motor circuit with a molecular atlas of its constituent MNs and uncovers organizing principles and conserved molecular codes of adult MN diversity.
first_indexed 2024-03-07T19:09:30Z
format Article
id doaj.art-953caea15b214f369b4db238ef9ec0ce
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-03-07T19:09:30Z
publishDate 2024-03-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj.art-953caea15b214f369b4db238ef9ec0ce2024-03-01T05:06:04ZengElsevierCell Reports2211-12472024-03-01433113857A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codesJayson J. Smith0Seth R. Taylor1Jacob A. Blum2Weidong Feng3Rebecca Collings4Aaron D. Gitler5David M. Miller, III6Paschalis Kratsios7Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USADepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA; Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USADepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USADepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USADepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USADepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA; Program in Neuroscience, Vanderbilt University, Nashville, TN 37240, USA; Corresponding authorDepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA; Corresponding authorSummary: Motor neurons (MNs) constitute an ancient cell type targeted by multiple adult-onset diseases. It is therefore important to define the molecular makeup of adult MNs in animal models and extract organizing principles. Here, we generate a comprehensive molecular atlas of adult Caenorhabditis elegans MNs and a searchable database. Single-cell RNA sequencing of 13,200 cells reveals that ventral nerve cord MNs cluster into 29 molecularly distinct subclasses. Extending C. elegans Neuronal Gene Expression Map and Network (CeNGEN) findings, all MN subclasses are delineated by distinct expression codes of either neuropeptide or transcription factor gene families. Strikingly, combinatorial codes of homeodomain transcription factor genes succinctly delineate adult MN diversity in both C. elegans and mice. Further, molecularly defined MN subclasses in C. elegans display distinct patterns of connectivity. Hence, our study couples the connectivity map of the C. elegans motor circuit with a molecular atlas of its constituent MNs and uncovers organizing principles and conserved molecular codes of adult MN diversity.http://www.sciencedirect.com/science/article/pii/S2211124724001852CP: Neuroscience
spellingShingle Jayson J. Smith
Seth R. Taylor
Jacob A. Blum
Weidong Feng
Rebecca Collings
Aaron D. Gitler
David M. Miller, III
Paschalis Kratsios
A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
Cell Reports
CP: Neuroscience
title A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
title_full A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
title_fullStr A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
title_full_unstemmed A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
title_short A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
title_sort molecular atlas of adult c elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
topic CP: Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2211124724001852
work_keys_str_mv AT jaysonjsmith amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT sethrtaylor amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT jacobablum amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT weidongfeng amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT rebeccacollings amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT aarondgitler amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT davidmmilleriii amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT paschaliskratsios amolecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT jaysonjsmith molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT sethrtaylor molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT jacobablum molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT weidongfeng molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT rebeccacollings molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT aarondgitler molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT davidmmilleriii molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes
AT paschaliskratsios molecularatlasofadultcelegansmotorneuronsrevealsancientdiversitydelineatedbyconservedtranscriptionfactorcodes