22 Papers found (0.012 seconds)

Ow MC et al. (2023) Epigenomes "Inheritance of Stress Responses via Small Non-Coding RNAs in Invertebrates and Mammals."

Hall SE, Ow MC

[

Epigenomes,

2023]

While reports on the generational inheritance of a parental response to stress have been widely reported in animals, the molecular mechanisms behind this phenomenon have only recently emerged. The booming interest in epigenetic inheritance has been facilitated in part by the discovery that small non-coding RNAs are one of its principal conduits. Discovered 30 years ago in the Caenorhabditis elegans nematode, these small molecules have since cemented their critical roles in regulating virtually all aspects of eukaryotic development. Here, we provide an overview on the current understanding of epigenetic inheritance in animals, including mice and C. elegans, as it pertains to stresses such as temperature, nutritional, and pathogenic encounters. We focus on C. elegans to address the mechanistic complexity of how small RNAs target their cohort mRNAs to effect gene expression and how they govern the propagation or termination of generational perdurance in epigenetic inheritance. Presently, while a great amount has been learned regarding the heritability of gene expression states, many more questions remain unanswered and warrant further investigation.

Ow MC et al. (2021) Elife "Somatic aging pathways regulate reproductive plasticity in Caenorhabditis elegans."

Hall SE, Nichitean AM, Ow MC

[

Elife,

2021]

In animals, early-life stress can result in programmed changes in gene expression that can affect their adult phenotype. In C. elegans nematodes, starvation during the first larval stage promotes entry into a stress-resistant dauer stage until environmental conditions improve. Adults that have experienced dauer (postdauers) retain a memory of early-life starvation that results in gene expression changes and reduced fecundity. Here we show that the endocrine pathways attributed to the regulation of somatic aging in C. elegans adults lacking a functional germline also regulate the reproductive phenotypes of postdauer adults that experienced early-life starvation. We demonstrate that postdauer adults reallocate fat to benefit progeny at the expense of the parental somatic fat reservoir and exhibit increased longevity compared to controls. Our results also show that the modification of somatic fat stores due to parental starvation memory is inherited in the F1 generation and may be the result of crosstalk between somatic and reproductive tissues mediated by the germline nuclear RNAi pathway.

Ow, M.C. et al. (2017) International Worm Meeting "Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans."

Hall, S.E., Borziak, K., Dorus, S., Ow, M.C.

[

International Worm Meeting,

2017]

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode, C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes that exhibit highly significant and opposite ("seesaw") transcriptional phenotypes in adults that entered dauer due to starvation (PDStv) compared to adults that entered dauer due to crowding (PDPhe), and are distinct from animals that bypassed dauer (CON). Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress, such that we observe a decrease or increase in PD/CON brood size for Stv or Phe conditions, respectively. In addition, we demonstrate that the observed seesaw gene expression and brood size differences require different signaling mechanisms for the Stv- and Phe-induced changes. The starvation program requires endocrine signaling and the germline, while the pheromone program is dependent on systemic RNAi signals from the soma. Interestingly, both transcriptional programs require the AGO CSR-1. Thus, signaling between the soma and the germline can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.

Ow MC et al. (2015) Methods Mol Biol "A Method for Obtaining Large Populations of Synchronized Caenorhabditis elegans Dauer Larvae."

Ow MC, Hall SE

[

Methods Mol Biol,

2015]

The C. elegans dauer is an attractive model with which to investigate fundamental biological questions, such as how environmental cues are sensed and are translated into developmental decisions through a series of signaling cascades that ultimately result in a transformed animal. Here we describe a simple method of using egg white plates to obtain highly synchronized purified dauers that can be used in downstream applications requiring large quantities of dauers or postdauer animals.

Ow MC et al. (2018) PLoS Genet "Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans."

Dorus S, Borziak K, Nichitean AM, Ow MC, Hall SE

[

PLoS Genet,

2018]

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw") transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.

Ow MC et al. (2008) Genes Dev "The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans."

Ambros V, Barrasa MI, Ow MC, Olsen PH, Martinez NJ, Walhout AJ, Conradt B, Silverman HS

[

Genes Dev,

2008]

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally via antisense base-pairing. Although miRNAs are involved in a variety of important biological functions, little is known about their transcriptional regulation. Using yeast one-hybrid assays, we identified transcription factors with a FLYWCH Zn-finger DNA-binding domain that bind to the promoters of several Caenorhabditis elegans miRNA genes. The products of the flh-1 and flh-2 genes function redundantly to repress embryonic expression of lin-4, mir-48, and mir-241, miRNA genes that are normally expressed only post-embryonically. Although single mutations in either flh-1 or flh-2 genes result in a viable phenotype, double mutation of flh-1 and flh-2 results in early larval lethality and an enhanced derepression of their target miRNAs in embryos. Double mutations in flh-2 and a third FLYWCH Zn-finger-containing transcription factor, flh-3, also result in enhanced precocious expression of target miRNAs. Mutations of lin-4 or mir-48&mir-241 do not rescue the lethal flh-1; flh-2 double-mutant phenotype, suggesting that the inviability is not solely the result of precocious expression of these miRNAs. Therefore, the FLH-1 and FLH-2 proteins likely play a more general role in regulating gene expression in embryos.

Ow MC et al. (2014) Methods Mol Biol "Small RNA library cloning procedure for deep sequencing of specific endogenous siRNA classes in Caenorhabditis elegans."

Lau NC, Ow MC, Hall SE

[

Methods Mol Biol,

2014]

In recent years, distinct classes of small RNAs ranging in size from ~21 to 26 nucleotides have been discovered and shown to play important roles in a wide array of cellular functions. Because of the abundance of these small RNAs, library preparation from an RNA sample followed by deep sequencing provides the identity and quantity of a particular class of small RNAs. In this chapter we describe a detailed protocol for preparing small RNA libraries for deep sequencing on the Illumina platform from the nematode C. elegans.

Ow MC et al. (2024) Front Mol Biosci "RNAi-dependent expression of sperm genes in ADL chemosensory neurons is required for olfactory responses in Caenorhabditis elegans."

Butcher RA, Hall SE, Ow MC, Nishiguchi MA, Dar AR

[

Front Mol Biosci,

2024]

Environmental conditions experienced early in the life of an animal can result in gene expression changes later in its life history. We have previously shown that C. elegans animals that experienced the developmentally arrested and stress resistant dauer stage (postdauers) retain a cellular memory of early-life stress that manifests during adulthood as genome-wide changes in gene expression, chromatin states, and altered life history traits. One consequence of developmental reprogramming in C. elegans postdauer adults is the downregulation of osm-9 TRPV channel gene expression in the ADL chemosensory neurons resulting in reduced avoidance to a pheromone component, ascr#3. This altered response to ascr#3 requires the principal effector of the somatic nuclear RNAi pathway, the Argonaute (AGO) NRDE-3. To investigate the role of the somatic nuclear RNAi pathway in regulating the developmental reprogramming of ADL due to early-life stress, we profiled the mRNA transcriptome of control and postdauer ADL in wild-type and nrde-3 mutant adults. We found 711 differentially expressed (DE) genes between control and postdauer ADL neurons, 90% of which are dependent upon NRDE-3. Additionally, we identified a conserved sequence that is enriched in the upstream regulatory sequences of the NRDE-3-dependent differentially expressed genes. Surprisingly, 214 of the ADL DE genes are considered "germline-expressed", including 21 genes encoding the Major Sperm Proteins and two genes encoding the sperm-specific PP1 phosphatases, GSP-3 and GSP-4. Loss of function mutations in gsp-3 resulted in both aberrant avoidance and attraction behaviors. We also show that an AGO pseudogene, Y49F6A.1 (wago-11), is expressed in ADL and is required for ascr#3 avoidance. Overall, our results suggest that small RNAs and reproductive genes program the ADL mRNA transcriptome during their developmental history and highlight a nexus between neuronal and reproductive networks in calibrating animal neuroplasticity.

Hresko MC et al. (1994) Worm Breeder's Gazette "Shoot First, Ask Questions Later"

Shrimankar PV, Waterston RH, Hresko MC

[

Worm Breeder's Gazette,

1994]

Shoot First, Ask Questions Later M.C Hresko, P.V. Shrimankar and R.H. Waterston. Washington Univ. Sch. of Med., St. Louis, MO 63110. coutu@sequencer.wustl.edu and pvs@elegans.wustl.edu

Edgley, Mark L. et al. (2021) MicroPubl Biol

Edgley, Mark L., Flibotte, Stephane, Moerman, Donald G

[

MicroPubl Biol,

2021]

We used whole-genome sequencing (WGS) data from a number of balanced lethal strains in Caenorhabditis elegans to show that the crossover suppressor qC1 is an inversion. The rearrangement is complex, with a large primary inversion that contains several other smaller inverted regions. The graphical representation below depicts these various qC1 rearrangements for ease of conceptualization. It is the simplest chromosomal structure compatible with the data currently available, but even then it is worth noting that the complexity of the qC1 chromosome can make the graphical reconstruction difficult to understand, and it may seem a bit like relativity theory or artwork from M.C. Escher (https://moa.byu.edu/m-c-eschers-relativity/).

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