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Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism

Ava Handley, Qiuli Wu, Tessa Sherry, Roger Pocock
doi: https://doi.org/10.1101/751339
Ava Handley
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia
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Qiuli Wu
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia
2Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School of Southeast University, Nanjing, China
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Tessa Sherry
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia
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Roger Pocock
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia
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  • For correspondence: roger.pocock@monash.edu
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SUMMARY

To maintain metabolic homeostasis, the nervous system must adapt and respond to an ever-changing environment. Transcription factors are key drivers of this adaptation, eliciting gene expression changes that can alter neuronal activity. Here we show in Caenorhabditis elegans that the terminal selector transcription factor ETS-5 not only establishes the identity of the BAG sensory neurons, but is re-purposed to shape the functional output of the BAG neurons post-mitotically. We find that ETS-5 directly regulates the expression of INS-1, an insulin-like peptide, in the BAG sensory neurons. INS-1 expression in the BAG neurons, and not in other INS-1-expressing neurons, decreases intestinal lipid levels and promotes foraging behaviour. Using in vivo analysis, we show that elevated intestinal lipid stores, driven by a high glucose diet, downregulates ETS-5-driven expression of INS-1. Together, our data reveal an inter-tissue regulatory loop by which a single neuron can control systemic metabolism, and that the activity of this neuron is modulated by the metabolic state of the organism.

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Posted August 31, 2019.
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Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism
Ava Handley, Qiuli Wu, Tessa Sherry, Roger Pocock
bioRxiv 751339; doi: https://doi.org/10.1101/751339
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Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism
Ava Handley, Qiuli Wu, Tessa Sherry, Roger Pocock
bioRxiv 751339; doi: https://doi.org/10.1101/751339

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