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

Elife. 2015 May 12:4:e06259. doi: 10.7554/eLife.06259.

Abstract

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 TGFβ 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 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron 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.

Keywords: C. elegans; dietary restriction; expression variability; gene regulation; neural circuit; neural code; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Eating / physiology
  • Gene Expression Regulation
  • Longevity / genetics*
  • Mutation
  • Nervous System / cytology
  • Nervous System / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Serotonin / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism
  • Tryptophan Hydroxylase / genetics*
  • Tryptophan Hydroxylase / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DAF-7 protein, C elegans
  • Transforming Growth Factor beta
  • Serotonin
  • Tryptophan Hydroxylase