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

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

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.

Show MeSH

Related in: MedlinePlus

Neuron-specific expression distributions in wild type and mutants.Distributions of NSM, ADF and ASI expression intensities in wild type, tph-1(−) mutants, daf-7(−) mutants and tph-1(−); daf-7(−) double mutants. Values represent the sum of the expression intensities in both cells of the neuron-pair.DOI:http://dx.doi.org/10.7554/eLife.06259.014
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4417936&req=5

fig5s1: Neuron-specific expression distributions in wild type and mutants.Distributions of NSM, ADF and ASI expression intensities in wild type, tph-1(−) mutants, daf-7(−) mutants and tph-1(−); daf-7(−) double mutants. Values represent the sum of the expression intensities in both cells of the neuron-pair.DOI:http://dx.doi.org/10.7554/eLife.06259.014

Mentions: (A) Food-responsive expression profiles of tph-1 in NSM (Ptph-1NSM) and ADF (Ptph-1ADF), and daf-7 in in ASI (Pdaf-7ASI) for different genetic backgrounds, as indicated in the legend. As in Figure 3, all values are normalized to the highest wildtype mean expression response observed in the respective neuron (dotted line). (B) Effects of tph-1 and daf-7 signalling on the dynamic range of food-induced expression modulation for tph-1 in NSM and ADF and daf-7 in ASI. The dynamic range (ΔF) is defined by the difference between the highest and lowest mean expression responses across the six food levels for each genotype. (C) Effects of tph-1 and daf-7 signalling on the inter-individual variability of expression responses as measured by the standard deviation of gene-expression distributions in each neuron. (D) Schematic of the total regulatory effects of tph-1 and daf-7 on both the dynamic range (ΔF) and variability and uncertainty (σ) of expression readouts to induce opposing effects on representational capability. Figure 5—figure supplement 1 shows the distributions of gene expression for Ptph-1NSM, Ptph-1ADF, and Pdaf-7ASI across all genotypes tested.


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

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Neuron-specific expression distributions in wild type and mutants.Distributions of NSM, ADF and ASI expression intensities in wild type, tph-1(−) mutants, daf-7(−) mutants and tph-1(−); daf-7(−) double mutants. Values represent the sum of the expression intensities in both cells of the neuron-pair.DOI:http://dx.doi.org/10.7554/eLife.06259.014
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417936&req=5

fig5s1: Neuron-specific expression distributions in wild type and mutants.Distributions of NSM, ADF and ASI expression intensities in wild type, tph-1(−) mutants, daf-7(−) mutants and tph-1(−); daf-7(−) double mutants. Values represent the sum of the expression intensities in both cells of the neuron-pair.DOI:http://dx.doi.org/10.7554/eLife.06259.014
Mentions: (A) Food-responsive expression profiles of tph-1 in NSM (Ptph-1NSM) and ADF (Ptph-1ADF), and daf-7 in in ASI (Pdaf-7ASI) for different genetic backgrounds, as indicated in the legend. As in Figure 3, all values are normalized to the highest wildtype mean expression response observed in the respective neuron (dotted line). (B) Effects of tph-1 and daf-7 signalling on the dynamic range of food-induced expression modulation for tph-1 in NSM and ADF and daf-7 in ASI. The dynamic range (ΔF) is defined by the difference between the highest and lowest mean expression responses across the six food levels for each genotype. (C) Effects of tph-1 and daf-7 signalling on the inter-individual variability of expression responses as measured by the standard deviation of gene-expression distributions in each neuron. (D) Schematic of the total regulatory effects of tph-1 and daf-7 on both the dynamic range (ΔF) and variability and uncertainty (σ) of expression readouts to induce opposing effects on representational capability. Figure 5—figure supplement 1 shows the distributions of gene expression for Ptph-1NSM, Ptph-1ADF, and Pdaf-7ASI across all genotypes tested.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus