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Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila

Dus, Monica and Lai, Jason Sih-Yu and Gunapala, Keith M. and Min, Soohong and Tayler, Timothy D. and Hergarden, Anne C. and Geraud, Eliot and Joseph, Christina M. and Suh, Greg S. B. (2015) Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila. Neuron, 87 (1). pp. 139-151. ISSN 0896-6273. PMCID PMC4697866. https://resolver.caltech.edu/CaltechAUTHORS:20150623-073200716

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[img] PDF (Document S1. Supplemental Experimental Procedures and Figures S1–S7) - Supplemental Material
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[img] Video (MPEG) (Movie S1. Exposure of the Brain to Nutritive D-glucose Activates Dh44 Neurons in Flies Carrying PDh44-GAL4 and UAS-GCaMP3.0, Related to Figure 3) - Supplemental Material
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[img] Video (MPEG) (Movie S2. Artificial Activation of Dh44R1 Neurons in PDh44R1-GAL4>TrpA1 Flies Results in an Increased Rate of Proboscis Extension, Related to Figure 5) - Supplemental Material
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[img] Video (MPEG) (Movie S3. Dh44 Peptide Stimulates the Gut Motility in Wild-Type Flies, Related to Figure 6) - Supplemental Material
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[img] Video (MPEG) (Movie S4. Dh44 Peptide Stimulates the Gut Motility in Wild-Type Flies, Related to Figure 6) - Supplemental Material
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[img] Video (MPEG) (Movie S5. Dh44 Peptide Has No Effect on the Gut Motility of MiDh44R2 Mutant, Related to Figure 6) - Supplemental Material
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[img] Video (MPEG) (Movie S6. Dh44 Peptide Has No Effect on the Gut Motility of MiDh44R2 Mutant, Related to Figure 6) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuron.2015.05.032DOIArticle
http://www.sciencedirect.com/science/article/pii/S0896627315004717PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697866PubMed CentralArticle
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.
Funders:
Funding AgencyGrant Number
NIH1K99DK097141
NIHRO1GM08946
National Institute on Deafness and Other Communication DisordersRO1DC01279
Irma T. Hirschl/Weill Caulier Trust AwardUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC4697866
Record Number:CaltechAUTHORS:20150623-073200716
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150623-073200716
Official Citation:Monica Dus, Jason Sih-Yu Lai, Keith M. Gunapala, Soohong Min, Timothy D. Tayler, Anne C. Hergarden, Eliot Geraud, Christina M. Joseph, Greg S.B. Suh, Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila, Neuron, Volume 87, Issue 1, 1 July 2015, Pages 139-151, ISSN 0896-6273, http://dx.doi.org/10.1016/j.neuron.2015.05.032. (http://www.sciencedirect.com/science/article/pii/S0896627315004717)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58430
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:23 Jun 2015 15:56
Last Modified:03 Oct 2019 08:35

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