title: A gene-expression-based neural code for food abundance that modulates lifespan.
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.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.
authors.forename: Eugeni V
authors.initials: EV
authors.lastname: Entchev
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.
authors.forename: Dhaval S
authors.initials: DS
authors.lastname: Patel
authors.affiliation: Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, United States.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhan
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Steele
authors.affiliation: Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, United States.
authors.forename: Hang
authors.initials: H
authors.lastname: Lu
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.
authors.forename: QueeLim
authors.initials: Q
authors.lastname: Ch'ng
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005786:Gene Expression Regulation; D008136:Longevity / Q000235:genetics*; D009154:Mutation; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D016212:Transforming Growth Factor beta; D012701:Serotonin; D014365:Tryptophan Hydroxylase
keywords: C. elegans; dietary restriction; expression variability; gene regulation; neural circuit; neural code; neuroscience