The Notch signaling pathway is best known for its role in cell fate specification during development. In a screen to identify genes required for octanol avoidance, we identified
osm-11, which encodes a secreted Notch ligand; we recently demonstrated that
osm-11 acts in C. elegans vulval development (WBPaper00032102). Here, we focus on the non-developmental role of
osm-11 in C. elegans behavior. The direct transcriptional targets of Notch signaling in neurons are unclear. By elucidating the mechanisms and targets of the Notch signaling pathway in the adult nervous system, we hope to provide insight into the complex regulation of adult behavior in animals. Here, we demonstrate that two behaviors are regulated by
osm-11 and Notch signaling: chemosensory response to octanol and quiescence. First, loss of
osm-11 results in a defective response to octanol. The two C. elegans'' Notch receptors, LIN-12 and GLP-1, act redundantly to regulate octanol response. Receptor function is required in adult animals in non-overlapping subsets of neurons. Additional components of the Notch signaling pathway are also required including
lst-1, a gene of unknown function that is a likely Notch target during development (WBPaper00006348). Overexpression of OSM-11 results in inappropriate quiescence of adult animals. This
osm-11 induced quiescence is reminiscent of that seen in satiety or molting, but
osm-11 induced quiescence is independent of feeding status.
osm-11 acts via Notch receptors in this behavior as well; perturbing either the LIN-12 or GLP-1 Notch receptor prevents quiescence.
osm-11 induced quiescence was also dependent on
egl-4, a cyclic GMP-dependent kinase, and the EGF receptor
let-23, two genes previously implicated in C. elegans behavioral quiescence (WBPaper00031383 and WBPaper00031030). Our genetic analysis places
egl-4 downstream of Notch, thus
egl-4 may be a direct Notch target. A previous bioinformatic analysis found numerous consensus binding sites for LAG-1 (a critical Notch pathway transcription factor) in
egl-4 intronic sequences. We are currently working to validate these and additional downstream targets of Notch. Notch function in the adult nervous system may be conserved across species.