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BMC Genomics,
2019]
BACKGROUND: Accumulation of protein aggregates are a major hallmark of progressive neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Transgenic Caenorhabditis elegans nematodes expressing the human synaptic protein -synuclein in body wall muscle show inclusions of aggregated protein, which affects similar genetic pathways as in humans. It is not however known how the effects of -synuclein expression in C. elegans differs among genetic backgrounds. Here, we compared gene expression patterns and investigated the phenotypic consequences of transgenic -synuclein expression in five different C. elegans genetic backgrounds. RESULTS: Transcriptome analysis indicates that -synuclein expression effects pathways associated with nutrient storage, lipid transportation and ion exchange and that effects vary depending on the genetic background. These gene expression changes predict that a range of phenotypes will be affected by -synuclein expression. We confirm this, showing that -synuclein expression delayed development, reduced lifespan, increased rate of matricidal hatching, and slows pharyngeal pumping. Critically, these phenotypic effects depend on the genetic background and coincide with the core changes in gene expression. CONCLUSIONS: Together, our results show genotype-specific effects and core alterations in both gene expression and in phenotype in response to -synuclein expression. We conclude that the effects of -synuclein expression are substantially modified by the genetic background, illustrating that genetic background needs to be considered in C. elegans models of neurodegenerative disease.
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Genes (Basel),
2020]
Different genetic backgrounds can modify the effect of mutated genes. Human -synuclein (<i>SNCA</i>) gene encodes -synuclein, and its oligomeric complexes accumulate with age and mediate the disruption of cellular homeostasis, resulting in the neuronal death that is characteristic of Parkinson's Disease. Polymorphic variants modulate this complex pathologic mechanism. Previously, we constructed five transgenic introgression lines of a <i>Caenorhabditis elegans</i> model of -synuclein using genetic backgrounds that are genetically diverse from the canonical wild-type Bristol N2. A gene expression analysis revealed that the -synuclein transgene differentially affects genome-wide transcription due to background modifiers. To further investigate how complex traits are affected in these transgenic lines, we measured the -synuclein transgene expression, the overall accumulation of the fusion protein of -synuclein and yellow fluorescent protein (YFP), the lysosome-related organelles, and the body size. By using quantitative PCR (qPCR), we demonstrated stable and similar expression levels of the -synuclein transgene in different genetic backgrounds. Strikingly, we observed that the levels of the a-synuclein:YFP fusion protein vary in different genetic backgrounds by using the COPAS biosorter. The quantification of the Nile Red staining assay demonstrates that -synuclein also affects lysosome-related organelles and body size. Our results show that the same -synuclein introgression in different <i>C. elegans</i> backgrounds can produces differing effects on complex traits due to background modifiers.
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J Cell Biol,
2019]
Wang studies lysosomal degradation pathways using <i>C. elegans</i> as a model system.
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[
Curr Biol,
2014]
Wang and Seydoux discuss the functional importance of P granules - the germline-specific RNA granules of C. elegans.
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Dev Cell,
2017]
In this issue of Developmental Cell, Dickinson etal. (2017) and Rodriguez etal. (2017), along with Wang etal. (2017) in Nature Cell Biology, show how PAR protein oligomerization can dynamically couple protein diffusion and transport by cortical flow to control kinase activity gradients and polarity in the C.elegans zygote.
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Dev Cell,
2017]
Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C.elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.
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Trends Genet,
2023]
Prenatal exposure to environmental agents can influence the fitness of not only the fetus, but also subsequent generations. In a recent study, Wang et al. demonstrated that feeding ursolic acid (UA), a plant-derived compound, to Caenorhabditis elegans mothers during their reproductive period prevented neurodegeneration in not only their offspring, but also the F2 progeny.
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Neuron,
2016]
Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C.elegans. In this issue of Neuron, Wang etal. (2016) report that C.elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive.
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[
STAR Protoc,
2022]
Live imaging is an important tool to track dynamic processes such as neuronal patterning events. Here, we describe a protocol for time-lapse microscopy analysis using neuronal migration and dendritic growth as examples. This protocol can provide detailed information for understanding cellular dynamics during postembryonic development in Caenorhabditis elegans (C. elegans). For complete details on the use and execution of this protocol, please refer to Feng etal. (2020), Li etal. (2021), and Wang etal. (2021).
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Bioessays,
2003]
Cell size is an important determinant of body size. While the genetic mechanisms of cell size regulation have been well studied in yeast, this process has only recently been addressed in multicellular organisms. One recent report by Wang et al. (2002) shows that in the nematode C. elegans, the TGFbeta-like pathway acts in the hypodermis to regulate cell size and consequently body size.((1)) This finding is an exciting step in discovering the molecular mechanisms that control cell and body size.