Sensory integration of food and population density during the diapause exit decision involves insulin-like signaling in Caenorhabditis elegans

Creators: Zhang, Mark G.¹; Seyedolmohadesin, Maedeh²; Mercado, Soraya Hawk¹; Tauffenberger, Arnaud³; Park, Heenam¹; Finnen, Nerissa¹; Schroeder, Frank C.³; Venkatachalam, Vivek²; Sternberg, Paul W.¹

1. California Institute of Technology
2. Northeastern University
3. Cornell University

Abstract

Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The Caenorhabditis elegans dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the Amphid Single Cilium J (ASJ) chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of ins-6 in the ASJ neurons integrates population density and food level and can reflect decision commitment since dauers committed to exiting have higher ins-6 expression levels than those of noncommitted dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that ins-6 expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution.

Copyright and License

Acknowledgement

Portions of the paper were developed from the Ph.D. thesis of M.G.Z. Plasmids containing TRPV1 and egl-4 cDNA were gifts from Cori Bargmann (The Rockefeller University, New York, NY). The ceh-36Δp::cmk-1(cDNA) plasmid was a kind gift from Piali Sengupta (Brandeis University, Waltham, MA). The pQZ::ins-6 plasmid was a kind gift from Joyce Alcedo (Wayne State University, Detroit, MI). KG#121[rab-3p::unc-31(cDNA)] was a gift from Kenneth Miller (Addgene plasmid # 110879) (Oklahoma Medical Research Foundation, Oklahoma City, OK). The strain JSR70 was a kind gift from Jagan Srinivasan (Worcester Polytechnic Institute, Worcester, MA). Some strains (SI Appendix, Table S1) were provided by the National BioResource Project, particularly from the lab of Shohei Mitani (Tokyo Women’s Medical University Institute for Integrated Medical Sciences, Tokyo, Japan), as well as the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). The strain KP9672 nuIs556[ptrx-1::GCaMP6.0s] was a kind gift from the Joshua Kaplan (Harvard Medical School, Boston, MA). Technical support was provided by members of the Sternberg lab including Barbara Perry, Stephanie Nava, and Wilber Palma. Microscopy assistance was provided by the Beckman Institute Biological Imaging Facility at Caltech. Critical feedback for the manuscript was provided by Sternberg lab members, particularly Hillel Schwartz and Nicholas Markarian. M.G.Z. was supported by a NIH Grant F31 NS120501-01. P.W.S. was supported by a Bren Professorship and by a NIH Grant R24-OD023041.

Contributions

M.G.Z., M.S., A.T., V.V., and P.W.S. designed research; M.G.Z., M.S., S.H.M., A.T., and N.F. performed research; M.G.Z., M.S., H.P., and F.C.S. contributed new reagents/analytic tools; M.G.Z. and M.S. analyzed data; and M.G.Z. and P.W.S. wrote the paper.

Data Availability

All study data are included in the article and/or SI Appendix.

Supplemental Material

Appendix 01

Files

zhang-et-al-2024-sensory-integration-of-food-and-population-density-during-the-diapause-exit-decision-involves-insulin.pdf

Files (3.4 MB)

Name	Size	Download all
zhang-et-al-2024-sensory-integration-of-food-and-population-density-during-the-diapause-exit-decision-involves-insulin.pdf md5:e7fe0f49db8187ab37b5ab74eacc0950	2.1 MB	Preview Download
pnas.2405391121.sapp.pdf md5:16fb69d80612d08af0454616ca685949	1.4 MB	Preview Download

	All versions	This version
Views	0	0
Downloads	0	0
Data volume	0 Bytes	0 Bytes