Language

English

Publication Date

1-7-2026

Journal

Genetics

DOI

10.1093/genetics/iyaf155

PMID

40794761

PMCID

PMC12774847

PubMedCentral® Posted Date

10-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Animals respond to changes in their environment and internal states via neuromodulation. Neuropeptides modulate neural circuits with flexibility because 1 gene can produce either multiple copies of the same neuropeptide or different neuropeptides. However, with this architectural complexity, the function of discrete and active neuropeptides is muddled. Here, we design a genetic tool that facilitates functional analysis of individual peptides. We engineered Escherichia coli bacteria to express active peptides, fed loss-of-function Caenorhabditis elegans, and rescued the activity of genes with varying lengths and functions: pdf-1, flp-3, ins-6, and ins-22. Some peptides were functionally redundant, while others exhibit unique and previously uncharacterized functions. We postulate our rescue-by-feeding approach can elucidate the functional landscape of neuropeptides, identifying the circuits and complex peptidergic pathways that regulate different behavioral and physiological processes.

Keywords

Animals, Caenorhabditis elegans, Escherichia coli, Neuropeptides, Caenorhabditis elegans Proteins

Published Open-Access

yes

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