A molecular atlas of adult C. elegans motor neurons reveals ancient diversity delineated by conserved transcription factor codes
Jayson J. Smith,
Seth R. Taylor,
Jacob A. Blum,
Weidong Feng,
Rebecca Collings,
Aaron D. Gitler,
David M. Miller, III,
Paschalis Kratsios
Affiliations
Jayson J. Smith
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA
Seth R. Taylor
Department 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, USA
Jacob A. Blum
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
Weidong Feng
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA
Rebecca Collings
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA
Aaron D. Gitler
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
David M. Miller, III
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA; Program in Neuroscience, Vanderbilt University, Nashville, TN 37240, USA; Corresponding author
Paschalis Kratsios
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA; Corresponding author
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.
