Neuronal Small RNAs Control Behavior Transgenerationally

It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous siRNAs and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small RNA-based mechanism for communication of neuronal processes transgenerationally. C. elegans worms expressing pan-neuronal rde-4 (generation P0) in a rde-4 mutant background, under the promoters Psng-1 and Prgef-1, and their rde-4 mutant progeny (generations F1-F3) were grown at 20 degrees on standard OP-50 bacteria. RNA was extracted from one day adult worms. We collected samples from whole animals, isolated neurons or gonads.