Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila
Abstract
Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars. Flies in which the activity of these neurons or the expression of Dh44 was disrupted failed to select nutritive sugars. Manipulation of the function of Dh44 receptors had a similar effect. Notably, artificial activation of Dh44 receptor-1 neurons resulted in proboscis extensions and frequent episodes of excretion. Conversely, reduced Dh44 activity led to decreased excretion. Together, these actions facilitate ingestion and digestion of nutritive foods. We propose that the Dh44 system directs the detection and consumption of nutritive sugars through a positive feedback loop.
Additional Information
© 2015 Elsevier Inc. Received: December 22, 2014. Revised: March 30, 2015. Accepted: May 7, 2015. Published: June 11, 2015. We thank Drs. Anne Simon, Justin Blau, Ann-Shyn Chiang, Paul Garrity, Dusan Zitnan, the Vienna Drosophila Resource Center (VDRC), and the Bloomington Drosophila Stock Center at Indiana University for fly stocks and reagents. We thank Drs. Jesus Torres-Vazquez, Steven Burden, Joel Belasco, and Niels Ringstad for allowing us to use equipments in their labs. We thank the G.S.B.S. lab and Drs. Jessica Treisman, Claude Desplan, and Gord Fishell for helpful comments on our manuscript. This work is supported by an NIH Career Development grant (National Institute of Diabetes and Digestive and Kidney Diseases grant 1K99DK097141) to M.D. and by NIH RO1 grants (National Institute of General Medical Sciences grant RO1GM08946 and National Institute on Deafness and Other Communication Disorders grant RO1DC01279), a Skirball Collaborative Award, and the Irma T. Hirschl/Weill Caulier Trust Award to G.S.B.S. Author Contributions: G.S.B.S., M.D., and J.S.-Y.L. designed, analyzed, and interpreted the experiments. G.S.B.S. wrote the manuscript with M.D. and other authors. M.D. performed the screen; all the behavioral experiments; immunostaining; and excretion, glycemia, and glycogen measurements. J.S.-Y.L. performed all the calcium-imaging experiments and immunostaining. K.M.G. made the PDh44R1-GAL4 and PDh44R2-GAL4 drivers and rescue constructs. S.M. showed DH44 neuronal projections in the gut. T.D.T. and A.C.H. constructed the neuropeptide GAL4 lines. E.G. and C.M.J. helped with the excretion measurement. G.S.B.S. conceived and supervised the project.Attached Files
Accepted Version - nihms693089.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.mp4
Supplemental Material - mmc3.mp4
Supplemental Material - mmc4.mp4
Supplemental Material - mmc5.mp4
Supplemental Material - mmc6.mp4
Supplemental Material - mmc7.mp4
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Additional details
- PMCID
- PMC4697866
- Eprint ID
- 58430
- DOI
- 10.1016/j.neuron.2015.05.032
- Resolver ID
- CaltechAUTHORS:20150623-073200716
- 1K99DK097141
- NIH
- RO1GM08946
- NIH
- RO1DC01279
- National Institute on Deafness and Other Communication Disorders
- Irma T. Hirschl/Weill Caulier Trust Award
- Created
-
2015-06-23Created from EPrint's datestamp field
- Updated
-
2022-06-03Created from EPrint's last_modified field