# Do unique homeobox gene codes define all neuron classes of the C. elegans nervous system?

> **NIH NIH F31** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $45,520

## Abstract

Project Summary
Despite our progress characterizing the molecular mechanisms by which post-mitotic neurons adopt their
terminal identity features, it remains unclear if there are any overarching themes in regulation of terminal nervous
system specification. In this grant proposal, I aim to analyze the function of a family of candidate regulators
throughout an entire nervous system. To do this, I make use of the relatively simple C. elegans nervous system,
which consists of 302 neurons in 118 anatomically distinct neurons classes. The mechanisms of neuronal identity
specification have been probed in C. elegans, where genetic mutant analysis has uncovered a host of
transcriptional regulators, designated terminal selectors. These terminal selectors control neuron-specific
features by binding to cis regulatory regions upstream of neuron-specific genes and regulating their transcription.
Of the terminal selectors that have been identified, most are homeodomain (HD) transcription factors belonging
to the homeobox gene family. The broad usage of homeobox genes suggests that HD transcription factors may
have evolutionarily ancient roles in specifying the terminal identity of an ancestral neuron type and, thus, I
hypothesize that HD transcription factors are required for specification of every neuron in the C. elegans nervous
system. To test this hypothesis, I propose analyzing the expression of more than 50 homeobox genes at a single
neuron resolution using reporter strains. Then, I aim to determine if those HD transcription factors act as terminal
selectors in the adult nervous system by examining the effect of their mutation on adoption of neurotransmitter
identity. Thus far, I have completed examination of 22 homeobox reporters and found 20 to be expressed in
post-mitotic neurons of the adult nervous system. One of those genes, ceh-34, was found to be a terminal
selector in all the neurons where it is expressed. These results suggest that the proposal will likely identify novel
regulators of terminal identity specification, and elucidate broad themes in development of post-mitotic neurons.

## Key facts

- **NIH application ID:** 9981026
- **Project number:** 5F31NS105398-03
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Molly Booth Reilly
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981026

## Citation

> US National Institutes of Health, RePORTER application 9981026, Do unique homeobox gene codes define all neuron classes of the C. elegans nervous system? (5F31NS105398-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9981026. Licensed CC0.

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