Thermosensory neuron dysfunction alters transposable element regulation

Transposable elements (TEs) can alter genome structure through transposition, and their activity is therefore tightly restricted by small RNA-mediated and chromatin-based silencing mechanisms. In C. elegans, elevated temperature can induce TE expression, raising the question of whether thermosensory neurons influence TE regulation. Here, we investigated the role of the AFD thermosensory neurons in TE regulation using multiple models of AFD dysfunction that altered TE expression; Mirage transposase induction emerged as the most reproducible phenotype across all AFD-dysfunctional strains. In the AFD triple mutant strain (PY9248), we observed strong Tc1 transposase expression, and genome-wide Tc1-enriched de novo insertions over generations. However, CRISPR reconstruction of the genotype in the N2 background did not reproduce the strong Tc1 phenotype, indicating that Tc1 activation and mutagenesis in PY9248 are background-associated rather than solely caused by loss of gcy-8, gcy-18, gcy-23 function. These findings support a model in which AFD neuron dysfunction reproducibly alters TE expression, particularly of Mirage, while heritable Tc1-mediated mutagenesis requires an additional, currently uncharacterized factor present in the AFD triple mutant background.