A rapid and massive gene expression shift marking adolescent transition in C. elegans

Snoek, L. Basten; Sterken, Mark G.; Volkers, Rita J. M.; Klatter, Mirre; Bosman, Kobus J.; Bevers, R.; Riksen, J.A.G.; Smant, G.; Cossins, Andrew R.; Kammenga, J.E.

doi:10.1038/srep03912

Cited by 43 publications

(82 citation statements)

References 33 publications

(72 reference statements)

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“…To untangle the developmental effects from the effects of the bar-1 mutation, we used a time-series dataset23. We showed that bar-1(ga80) results in a slower development, as these worms take on average ~10% more time to develop than Bristol N2.…”

Section: Resultsmentioning

confidence: 99%

Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans

Bent

Sterken

Volkers

et al. 2014

Sci Rep

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C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.

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Section: Resultsmentioning

confidence: 99%

Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans

Bent

Sterken

Volkers

et al. 2014

Sci Rep

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“…The phenotype of N2 is distinct from wild strains in several ways, including aggregation behavior, maturation time, fecundity, body size, and many other traits [26, 27, 29, 36–43]. The atmospheric oxygen concentration on agar plates is substantially higher than levels preferred by wild strains [44–46], and laboratory oxygen concentration is a strong selective pressure on the organism.…”

Section: Selective Pressures: Nature Versus Laboratorymentioning

confidence: 99%

The laboratory domestication of Caenorhabditis elegans

Sterken¹,

Snoek²,

Kammenga³

et al. 2015

Trends in Genetics

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Model organisms are of great importance to understanding basic biology and to making advances in biomedical research. However, the influence of laboratory cultivation on these organisms is underappreciated, especially how that environment can affect research outcomes. Recent experiments led to insights into how the widely used laboratory reference strain of the nematode Caenorhabditis elegans compares to natural strains. Here, we describe potential selective pressures that led to fixation of laboratory-derived alleles for the genes npr-1, glb-5, and nath-10. These alleles influence a large number of traits, resulting in behaviors that affect experimental interpretations. Furthermore, strong phenotypic effects caused by these laboratory-derived alleles hinder the discovery of natural alleles. We highlight strategies to reduce the influences of laboratory-derived alleles and to harness the full power of C. elegans.

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“…After cooling on ice for 1 min, the samples were pipetted into the cartridges, and the protocol as recommended by Promega was continued. After mRNA isolation, the "Two-color Microarray-based Gene Expression Analysis, Low Input Quick Amp Labeling" protocol, version 6.0, was followed, starting from step 5 (4,30,31).…”

Section: Methodsmentioning

confidence: 99%

Natural Genetic Variation Differentially Affects the Proteome and Transcriptome in Caenorhabditis elegans

Kamkina

Snoek

Grossmann

et al. 2016

Molecular & Cellular Proteomics

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Natural genetic variation is the raw material of evolution and influences disease development and progression. An important question is how this genetic variation translates into variation in protein abundance. To analyze the effects of the genetic background on gene and protein expression in the nematode Caenorhabditis elegans, we quantitatively compared the two genetically highly divergent wild-type strains N2 and CB4856. Gene expression was analyzed by microarray assays, and proteins were quantified using stable isotope labeling by amino acids in cell culture. Among all transcribed genes, we found 1,532 genes to be differentially transcribed between the two wild types. Of the total 3,238 quantified proteins, 129 proteins were significantly differentially expressed between N2 and CB4856. The differentially expressed proteins were enriched for genes that function in insulin-signaling and stress-response pathways, underlining strong divergence of these pathways in nematodes. The protein abundance of the two wild-type strains correlates more strongly than protein abundance versus transcript abundance within each wild type. Our findings indicate that in C. elegans only a fraction of the changes in protein abundance can be explained by the changes in mRNA abundance. These findings corroborate with the observations made across species. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052548, 1670-1680, 2016.Natural genetic variation in gene expression shapes the diversity in phenotypic traits and is the raw material for evolutionary processes (1). Variation in gene expression can be very extensive across individuals with different genotypes. The additive effects (narrow-sense heritability) of independent loci on gene expression variation can reach 35% in humans (2). The broad-sense heritable variation in gene expression has been estimated to be up to 70% in the nematode Caenorhabditis elegans (3, 4) and up to 80% in yeast (5). This high heritability and the ability to construct genetically segregating populations facilitate mapping of gene expression regulation and subsequent detection of expression quantitative trait loci (eQTL) 1 (5-11). eQTLs are genomic regions containing a polymorphism associated with variation in transcript abundance between genotypes (12). eQTL analysis provides insight into the underlying genetic architecture of complex traits and is valuable for the identification of pathways and gene networks (10,(13)(14)(15). A key question is whether gene expression variation is translated into variation at the proteome level and whether it affects functionally relevant proteins. Genetic model species provide an ideal platform to explore the relationship between gene expression variation and variation at the proteome level due to their tractability. Although it is well established that there is a correlation between transcript and protein abundances, the relationship between natural variation in gene expression and variation in protein abundance is less well understood. The proteome provides informat...

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A rapid and massive gene expression shift marking adolescent transition in C. elegans

Cited by 43 publications

References 33 publications

Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans

Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans

The laboratory domestication of Caenorhabditis elegans

Natural Genetic Variation Differentially Affects the Proteome and Transcriptome in Caenorhabditis elegans

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