Posner, Rachel et al. (2017) International Worm Meeting "Gene regulation via non-cell autonomous acting small RNAs in C. elegans."

Azmon, Eran, Star, Ekaterina, Anava, Sarit, Rechavi, Oded, Posner, Rachel, Hobert, Oliver, Gingold, Hila, Bracha, Shahar

[International Worm Meeting, 2017]

Exposure of C. elegans to artificial dsRNA can trigger exogenous small RNA-mediated silencing that transmits from somatic cells to the germline, and persists for multiple generations. However, it is unknown whether endogenous types of small RNAs (miRNAs, piRNAs and endo-siRNAs) produce systematic responses and what type of effect they may have on gene regulation. Our recent results suggest that endogenous siRNAs act in a non-cell autonomous manner, orchestrating gene silencing between tissues. We will present a dissection of the major components of the RNAi pathway required for non-cell autonomous gene regulation by endo-siRNAs and provide evidence possibly linking the regulation of physiological phenotypes to small RNAs mobilizing between tissues.

Edwards, Tyson et al. (2015) International Worm Meeting "Dopamine induces circling locomotion in C. elegans."

Edwards, Tyson, Bai, Jihong, Han, Bicheng

[International Worm Meeting, 2015]

Navigational circling bias occurs in various animal species, including humans1, and has been linked to dopamine signaling 2,3. We have observed a unique circling behavior in wild type worms exposed to low concentrations of exogenous dopamine. Interestingly, this behavior is phenocopied by administration of 3,4-methylenedioxymethamphetamine (MDMA, a.k.a. "ecstasy")4. We find that dopamine induces ventrally-directed circles in a dose-dependent manner. We hypothesize that distinct neurons in the locomotory circuit have differing sensitivities to dopamine, resulting in asymmetric neurotransmission that biases locomotion. Indeed, laser ablation of a subset of inhibitory motor neurons induces circling5. This subset of motor neurons may be sensitized by expression of an inhibitory dopamine receptor. Dopamine mutants that lack the canonical D2-like receptor dop-3 retain the ability to circle, suggesting that a novel receptor may be involved. We are working to identify the putative receptor, and to implement calcium imaging and electrophysiological methods to determine the circuits that mediate circling locomotion. Overall, this work hopes to shed light on the mechanisms by which neuromodulators target specific circuits to alter behavior.1. Souman, J. L., Frissen, I., Sreenivasa, M. N. & Ernst, M. O. Walking Straight into Circles. Curr. Biol. 19, 1538-1542 (2009).2. Bracha, H. S., Shults, C., Glick, S. D. & Kleinman, J. E. Spontaneous asymmetric circling behavior in hemi-parkinsonism; a human equivalent of the lesioned-circling rodent behavior. Life Sci. 40, 1127-1130 (1987).3. Mohr, C., Landis, T., Bracha, H. S., Fathi, M. & Brugger, P. Human locomotion: levodopa keeps you straight. Neurosci. Lett. 339, 115-118 (2003).4. Schreiber, M. A. & McIntire, S. L. A Caenorhabditis elegans p38 MAP kinase pathway mutant protects from dopamine, methamphetamine, and MDMA toxicity. Neurosci. Lett. 498, 99-103 (2011).5. Donnelly, J. L. et al. Monoaminergic Orchestration of Motor Programs in a Complex C. elegans Behavior. PLoS Biol 11, e1001529 (2013).