# Discovery and analysis of the C. elegans neuronal gene expression network (CENGEN)

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $1,242,113

## Abstract

PROJECT SUMMARY
There is a current lack of understanding of differential gene expression within the nervous system. Ideally one
would like to know, across all neuron types, exactly how the genome is transcribed and processed into
functional RNAs. This information is fundamentally important because differential gene expression defines the
form and function of individual neurons, determines how individual neurons contribute to circuit physiology and
behavior, and influences how individual neurons are affected by injury and disease. Further, detailed and
complete knowledge of differential gene expression within the nervous system would help elucidate the logic
and cellular mechanisms that generate neuronal diversity, including regulation of gene expression, alternative
splicing, and miRNA function. Yet progress in this area has been limited: For most nervous systems, the exact
number of distinct types of neurons is unknown and therefore a global map of neuron-specific gene expression
is not achievable. Here we propose to address this problem in a project to discover and analyze the C. elegans
Neuronal Gene Expression Map & Network (CeNGEN). The C. elegans nervous system contains precisely 302
total neurons comprising 118 classes of distinct neuronal types. We propose to exploit this unique attribute to
analyze gene expression with high accuracy in every individual neuronal type. CeNGEN proceeds in four
specific aims. Aim 1) Establish 118 transgenic strains, each one expressing fluorescent markers that uniquely
label a single type of neuron. Aim 2) Use innovative cell dissociation and FACS methods to isolate each type of
neuron from age-matched adults, and use RNA-seq approaches to assess global coding transcript and miRNA
expression, as well as splicing diversity. Aim 3) Utilize single cell sequencing technology to precisely map gene
expression over multiple parameter spaces. Aim 4) Build cell-centered and gene-centered expression maps,
and seek connections with other uniquely known features of the C. elegans nervous system including the
wiring diagram, the cell lineage, neurotransmitter identity, and function. CeNGEN represents a paradigmatic
advance in neurogenetics, and provides a unique opportunity to elucidate the global control of neuron-specific
gene expression and to relate gene expression to neuronal wiring and function. Expected significant outcomes
include: Identification of conserved regulatory mechanisms that generate neuronal specificity and diversity;
Detailed understanding of alternative splicing and miRNA function across the nervous system; Relationship of
differential gene expression to neuronal lineage, anatomy, function and connectivity. CeNGEN will also serve
as a resource for future studies in C. elegans neuroscience, and will provide a framework for addressing global
differential gene expression in more complex nervous systems that are currently not amenable to this
comprehensive approach.

## Key facts

- **NIH application ID:** 9990899
- **Project number:** 5R01NS100547-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MARC HAMMARLUND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,242,113
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990899

## Citation

> US National Institutes of Health, RePORTER application 9990899, Discovery and analysis of the C. elegans neuronal gene expression network (CENGEN) (5R01NS100547-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990899. Licensed CC0.

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