Periphery signals generated by Piezo-mediated stomach stretch and Neuromedin-mediated glucose load regulate the Drosophila brain nutrient sensor

Yangkyun Oh, Jason Sih Yu Lai, Soohong Min, Huai Wei Huang, Stephen D. Liberles, Hyung Don Ryoo, Greg S.B. Suh

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Nutrient sensors allow animals to identify foods rich in specific nutrients. The Drosophila nutrient sensor, diuretic hormone 44 (DH44) neurons, helps the fly to detect nutritive sugar. This sensor becomes operational during starvation; however, the mechanisms by which DH44 neurons or other nutrient sensors are regulated remain unclear. Here, we identified two satiety signals that inhibit DH44 neurons: (1) Piezo-mediated stomach/crop stretch after food ingestion and (2) Neuromedin/Hugin neurosecretory neurons in the ventral nerve cord (VNC) activated by an increase in the internal glucose level. A subset of Piezo+ neurons that express DH44 neuropeptide project to the crop. We found that DH44 neuronal activity and food intake were stimulated following a knockdown of piezo in DH44 neurons or silencing of Hugin neurons in the VNC, even in fed flies. Together, we propose that these two qualitatively distinct peripheral signals work in concert to regulate the DH44 nutrient sensor during the fed state.

Original languageEnglish
Pages (from-to)1979-1995.e6
JournalNeuron
Volume109
Issue number12
DOIs
StatePublished - 16 Jun 2021

Bibliographical note

Funding Information:
We thank Dr. Nilay Yapici and Sam Whitehead for providing the python-based customized program for analyzing Expresso feeding data. We thank Drs. Jan A. Veenstra, Michael J. Pankratz, and Ernst Hafen, as well as the Vienna Drosophila Resource Center (VDRC) and Bloomington Drosophila Stock Center, for fly stocks and reagents. We also thank Drs. Gary J. Schwartz, Jessica E. Treisman, Erika Bach, Niels Ringstad, and Nicholas Stavropoulos and the Ryoo and Suh laboratory members for stimulating discussion and comments on the paper. This work is supported by American Heart Association grant 20POST35210914 to S.M.; the Howard Hughes Medical Institute (S.D.L.); NIH R01 grants R01DK116294 and R01DK106636 to G.S.B.S. which have been transferred to H.D.R.; KAIST Chancellor's fund and grants from the Samsung Science and Technology Foundation (project SSTF-BA-1802-11); National Research Foundation of Korea grant NRF-2020R1A2C2009865 to G.S.B.S.; and the NRF funded by Ministry of Science and ICT (2021M3F3A2A01037365). Y.O. performed calcium imaging, immunohistochemistry, Expresso feeding assay, two-choice assay, DH44 secretion assay, statistical analyses, and figure design. J.S.-Y.L. carried out the pilot in vivo calcium imaging to determine candidate signals that inhibit DH44 neurons. S.M. and S.D.L. provided piezo mutant and isogenic control flies. H.-W.H. performed qPCR to measure the expression level of hugin gene in fed or starved flies. H.D.R. and G.S.B.S. supervised the project. Y.O. and G.S.B.S. conceived the project and wrote the manuscript with input from other authors. The authors declare no competing interests.

Funding Information:
We thank Dr. Nilay Yapici and Sam Whitehead for providing the python-based customized program for analyzing Expresso feeding data. We thank Drs. Jan A. Veenstra, Michael J. Pankratz, and Ernst Hafen, as well as the Vienna Drosophila Resource Center (VDRC) and Bloomington Drosophila Stock Center, for fly stocks and reagents. We also thank Drs. Gary J. Schwartz, Jessica E. Treisman, Erika Bach, Niels Ringstad, and Nicholas Stavropoulos and the Ryoo and Suh laboratory members for stimulating discussion and comments on the paper. This work is supported by American Heart Association grant 20POST35210914 to S.M.; the Howard Hughes Medical Institute (S.D.L.); NIH R01 grants R01DK116294 and R01DK106636 to G.S.B.S., which have been transferred to H.D.R.; KAIST Chancellor’s fund and grants from the Samsung Science and Technology Foundation (project SSTF-BA-1802-11 ); National Research Foundation of Korea grant NRF-2020R1A2C2009865 to G.S.B.S.; and the NRF funded by Ministry of Science and ICT ( 2021M3F3A2A01037365 ).

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • DH44 neurons
  • Drosophila
  • Hugin
  • Neuromedin U
  • Piezo channel
  • carbohydate feeding
  • glucose-excited neuron
  • mechanosensation
  • nutrient sensor
  • satiety signal

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