No abstract

SummaryNervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches 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 unique codes of ∼23 neuropeptide-encoding genes and ∼36 neuropeptide receptors thus pointing to an expansive “wireless” signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at 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.

A single neuron and its synapses define the fundamental structural motif of the brain but the underlying gene expression programs that specify individual neuron types are poorly understood.To address this question in a model organism, we have produced a gene expression profile of >90% of the individual neuron classes in the C. elegans nervous system, an ensemble of neurons for which both the anatomy and connectivity are uniquely defined at single cell resolution. We generated single cell transcriptomes for 52,412 neurons that resolve as clusters corresponding to 109 of the canonical 118 neuron classes in the mature hermaphrodite nervous system. Detailed analysis revealed molecular signatures that further subdivide identified classes into specific neuronal subtypes. Notably, neuropeptide-related genes are often differentially expressed between subtypes of the given neuron class which points to distinct functional characteristics.All of these data are publicly available at our website (http://www.cengen.org) and can be interrogated at the web application SCeNGEA (https://cengen.shinyapps.io/SCeNGEA). We expect that this gene expression catalog will spur the goal of delineating the underlying mechanisms that define the developmental lineage, detailed anatomy, synaptic connectivity and function of each type of C. elegans neuron.

SUMMARY During nervous system development, postmitotic neurons face the challenge of generating and structurally organizing specific synapses with appropriate synaptic partners. An important unexplored question is whether the process of synaptogenesis is coordinated with the adoption of specific signaling properties of a neuron. Such signaling properties are defined by the neurotransmitter system that a neuron uses to communicate with postsynaptic partners, by the neurotransmitter receptor type used to receive input from presynaptic neurons and, potentially, by other sensory receptors that activate a neuron. Elucidating the mechanisms that coordinate synaptogenesis, neuronal activation and neurotransmitter signaling in a postmitotic neuron represents one key approach to understand how neurons develop as functional units. Using the SAB class of Caenorhabditis elegans motor neurons as a model system, we show here that the phylogenetically conserved COE-type transcription factor UNC-3 is required for synaptogenesis. UNC-3 directly controls the expression of the ADAMTS-like protein MADD-4/Punctin, a presynaptically secreted synapse-organizing molecule that clusters postsynaptic receptors. UNC-3 also controls the assembly of presynaptic specializations and ensures the coordinated expression of enzymes and transporters that define the cholinergic neurotransmitter identity of the SAB neurons. Furthermore, synaptic output properties of the SAB neurons are coordinated with neuronal activation and synaptic input, as evidenced by UNC-3 also regulating the expression of ionotropic neurotransmitter receptors and putative stretch receptors. Our study shows how synaptogenesis and distinct, function-defining signaling features of a postmitotic neuron are hardwired together through coordinated transcriptional control.