4.8 Article

A gene-expression-based neural code for food abundance that modulates lifespan

Journal

ELIFE
Volume 4, Issue -, Pages -

Publisher

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.06259

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Funding

  1. Wellcome Trust [087146]
  2. Biotechnology and Biological Sciences Research Council (BBSRC) [BB/H020500/1]
  3. European Research Council [NeuroAge 242666]
  4. National Institutes of Health [R01GM088333, R01AG035317]
  5. National Science Foundation [0954578, 0946809 GRFP]
  6. National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
  7. BBSRC [BB/H020500/1] Funding Source: UKRI
  8. MRC [G0901899] Funding Source: UKRI
  9. Biotechnology and Biological Sciences Research Council [BB/H020500/1] Funding Source: researchfish
  10. Medical Research Council [G0901899] Funding Source: researchfish
  11. Directorate For Engineering
  12. Div Of Chem, Bioeng, Env, & Transp Sys [0954578] Funding Source: National Science Foundation

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How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGF beta and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGF beta) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGF beta and serotonin signaling to tune the accuracy of this multineuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

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