Universität zu Köln

Szántó, Péter Richárd (2025). Thermosensory Neurons Control Germline Transposons and Modulate Genetic Inheritance. PhD thesis, Universität zu Köln.

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Abstract

Transposable elements (TEs) constitute a significant portion of the genome and pose both evolutionary driver potential and mutagenic threat. In the germline, small RNA (sRNA) pathways act as critical repressors of TE activity, safeguarding genome integrity across generations. Traditionally, it has been assumed that somatic signals cannot influence the germline genome, a concept rooted in August Weismann’s barrier. However, recent discoveries in epigenetic inheritance have begun to challenge this view by demonstrating that environmental signals sensed by somatic tissues can modulate germline gene expression. The central aim of my study was to test whether neuronal sensing of heat stress in Caenorhabditis elegans (C. elegans) can influence germline TE activity, thereby altering genetic inheritance. Specifically, I investigated the role of the AFD thermosensory neuron in regulating TE silencing and mobilization. Using models of AFD neuron dysfunction, I demonstrated that disruption of thermosensory neuron leads to TE desilencing in germ cells. This results in de novo insertions of the Tc1 TE family, and an increased frequency of heritable mutations. These findings reveal a noncell- autonomous regulation linking somatic neuron activity to induce mutations in the germline genome, thereby breaching the Weismann barrier. Exploratory transcriptomic and proteomic analyses identified two potential parallel stressresponsive pathways downstream of AFD function that converge on the inhibition of germ line specific sRNA pathways, leading to transposon derepression. Preliminary experimental data show that tph-1 mutants exhibit elevated TE activation under heat stress, while pmk-1 mutants display reduced TE induction, supporting their respective roles as positive and negative regulators of TE expression. These findings suggest a neuro-germline communication axis that modulates TE silencing in response to environmental stress. In the second part of this study, I investigated the role of age-related TE activation, which has been proposed to drive genomic instability and inflammaging, contributing to both somatic and reproductive aging. To assess whether TE activity influences these processes, I applied a pharmacological approach using the TE inhibitor raltegravir. The treatment enhanced fertility, maintained germline integrity, and reduced reproductive abnormalities, especially under heat stress. These results suggest that pharmacological inhibition of TE activity may offer a promising strategy to support reproductive health and promote healthy aging.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Szántó, Péter Richárd szanpet96hu@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-796967
Date:	2025
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Natural sciences and mathematics Life sciences
Uncontrolled Keywords:	Keywords Language Transposable elements English Inheritance English Germ line English
Date of oral exam:	11 August 2025
Referee:	Name Academic Title Schumacher, Björn Prof. Dr. Hoppe, Thorsten Prof. Dr. Gehring, Niels Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79696