Maternal age modulates progeny social behavior via a small RNA–neuropeptide axis

Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in Caenorhabditis elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of older mothers display reduced neuronal responses and weaker repulsion. We identified an ERI-1–microRNA–neuropeptide signaling axis operating in peptidergic AVH interneurons that modulates ADL circuit responsiveness. ERI-1 promotes expression of the neuropeptide gene flp-26 by repressing mir-8207 , and signaling from AVH to ADL establishes pheromone sensitivity. Maternal aging is associated with reduced ERI-1 expression in progeny AVH neurons and dampening this signaling pathway. Consequently, progeny of young mothers, though developmentally less robust, disperse more readily from crowded, pheromone-rich environments, offsetting their early-life disadvantages. Our findings reveal a molecular and circuit-level mechanism by which maternal physiology adaptively configures offspring neural computation and behavioral strategy across generations.

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Publication Details

Journal
Genes & Development
Published
2026-10-29
DOI
https://doi.org/10.1101/gad.353774.126
Primary Topic
Neurobiology and Insect Physiology Research
Type
preprint

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preprint

Maternal age modulates progeny social behavior via a small RNA–neuropeptide axis

Rebecca A. Butcher, Jinkwang Kim, Sejoo Jeong, Hyeonjeong Hwang et al.
Genes & Development
Neurobiology and Insect Physiology Research
preprint

Maternal age modulates progeny social behavior via a small RNA–neuropeptide axis

Rebecca A. Butcher, Jinkwang Kim, Sejoo Jeong, Hyeonjeong Hwang, Kyuhyung Kim, YongJin Cheon, Seung Hee Oh, Taehyun A Kim, Semin Hwangbo, Sujin Jo, Eujeong Oh, Jong-Chan Lee, Abdul Rouf Dar
preprint en

Abstract

Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in Caenorhabditis elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of older mothers display reduced neuronal responses and weaker repulsion. We identified an ERI-1–microRNA–neuropeptide signaling axis operating in peptidergic AVH interneurons that modulates ADL circuit responsiveness. ERI-1 promotes expression of the neuropeptide gene flp-26 by repressing mir-8207 , and signaling from AVH to ADL establishes pheromone sensitivity. Maternal aging is associated with reduced ERI-1 expression in progeny AVH neurons and dampening this signaling pathway. Consequently, progeny of young mothers, though developmentally less robust, disperse more readily from crowded, pheromone-rich environments, offsetting their early-life disadvantages. Our findings reveal a molecular and circuit-level mechanism by which maternal physiology adaptively configures offspring neural computation and behavioral strategy across generations.

Genes & Development
Daegu Gyeongbuk Institute of Science and Technology (KR), University of Florida (US), Gwangju Institute of Science and Technology (KR)
Korea Brain Research Institute, National Research Foundation of Korea, Daegu Gyeongbuk Institute of Science and Technology, National Institutes of Health, Office of Research Infrastructure Programs, National Institutes of Health
Neurobiology and Insect Physiology Research
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