Gonad-soma inter-tissue communication alleviates ultraviolet-induced neurotoxicity in C. elegans.
7 affiliations
- 1Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.
- 2University of Science and Technology of China, Hefei, China.
- 3Institute of Radiation Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
- 4Institute of Radiation Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. [email protected].
- 5Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. [email protected].
- 6Institute of Radiation Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. [email protected].
- 7Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. [email protected].
Abstract
Organismal genome stability is constantly challenged by endogenous and exogenous genotoxins, and DNA damage response (DDR) is a classical cell-autonomous mechanism for counteracting such damage. It remains unclear how somatic cells with DDR deficiencies maintain genomic integrity under stress. This study investigated whether inter-tissue communication, particularly from the reproductive system, coordinates DNA damage repair in repair-deficient cells. Using Caenorhabditis elegans, in which certain upstream DDR signaling components are transcriptionally repressed in somatic cells, we examined UV-induced neurotoxicity through behavioral assays (head thrashes, body bends, foraging, and salt chemotaxis). These deficits were associated with preferential impairment of dopaminergic, glutamatergic, and serotonergic reporter readouts, along with heterogeneous transcriptional remodeling of neurotransmitter pathway and pan-neuronal synaptic genes. Deficiencies in upstream DDR signaling (ATM/ATR), whether systemic or germline-specific, significantly exacerbated UV-induced neurobehavioral and transcriptional deficits. In contrast, germline-specific loss of nucleotide excision repair (NER) machinery had no significant effect, highlighting a unique inter-tissue signaling role for upstream DDR. Furthermore, CPR-4 was identified as a key mediator of this inter gonad-soma signaling. Germline DDR activation regulated cpr-4 expression, and loss of CPR-4 abolished UV-induced transcriptional activation of the somatic NER pathway and heightened behavioral sensitivity. Our study revealed a novel germline DDR to somatic tissue signaling axis essential for organismal stress resilience and proposed a new regulatory model centered on gonad-soma signaling.
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BibTeX
@article{zhang2026gonadsoma,
title = {{Gonad-soma inter-tissue communication alleviates ultraviolet-induced neurotoxicity in C. elegans.}},
author = {Wenjing Zhang and Liu Ding and Shanpeng Qiao and Jiyu Xu and Qiyi Yi and Binmei Liu and Po Bian and Ting Wang},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03095-5},
url = {https://europepmc.org/article/MED/42897529},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gonad-soma inter-tissue communication alleviates ultraviolet-induced neurotoxicity in C. elegans.
AU - Wenjing Zhang
AU - Liu Ding
AU - Shanpeng Qiao
AU - Jiyu Xu
AU - Qiyi Yi
AU - Binmei Liu
AU - Po Bian
AU - Ting Wang
PY - 2026
DA - 2026/07/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03095-5
UR - https://europepmc.org/article/MED/42897529
AB - Organismal genome stability is constantly challenged by endogenous and exogenous genotoxins, and DNA damage response (DDR) is a classical cell-autonomous mechanism for counteracting such damage. It remains unclear how somatic cells with DDR deficiencies maintain genomic integrity under stress. This study investigated whether inter-tissue communication, particularly from the reproductive system, coordinates DNA damage repair in repair-deficient cells. Using Caenorhabditis elegans, in which certain upstream DDR signaling components are transcriptionally repressed in somatic cells, we examined UV-induced neurotoxicity through behavioral assays (head thrashes, body bends, foraging, and salt chemotaxis). These deficits were associated with preferential impairment of dopaminergic, glutamatergic, and serotonergic reporter readouts, along with heterogeneous transcriptional remodeling of neurotransmitter pathway and pan-neuronal synaptic genes. Deficiencies in upstream DDR signaling (ATM/ATR), whether systemic or germline-specific, significantly exacerbated UV-induced neurobehavioral and transcriptional deficits. In contrast, germline-specific loss of nucleotide excision repair (NER) machinery had no significant effect, highlighting a unique inter-tissue signaling role for upstream DDR. Furthermore, CPR-4 was identified as a key mediator of this inter gonad-soma signaling. Germline DDR activation regulated cpr-4 expression, and loss of CPR-4 abolished UV-induced transcriptional activation of the somatic NER pathway and heightened behavioral sensitivity. Our study revealed a novel germline DDR to somatic tissue signaling axis essential for organismal stress resilience and proposed a new regulatory model centered on gonad-soma signaling.
SN - 1478-811X
ER -