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J Cell Sci,
2002]
Recent studies have characterised a family of giant cytoskeletal crosslinkers encoded by the short stop gene in Drosophila and the dystonin/BPAG1 and MACF1 genes in mammals. We refer to the products of these genes as spectraplakins to highlight the fact that they share features with both the spectrin and plakin superfamilies. These genes produce a variety of large proteins, up to almost 9000 residues long, which can potentially extend 0.4 micro m across a cell. Spectraplakins can interact with all three elements of the cytoskeleton: actin, microtubules and intermediate filaments. The analysis of mutant phenotypes in BPAG1 in mouse and short stop in Drosophila demonstrates that spectraplakins have diverse roles. These include linking the plasma membrane and the cytoskeleton, linking together different elements of the cytoskeleton and organising membrane domains.
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WormBook,
2005]
Cell-cell interactions mediated by the Notch signaling pathway occur throughout C. elegans embryogenesis. These interactions have major roles in specifying cell fates and in tissue morphogenesis. The network of Notch interactions is linked in part through the Notch-regulated expression of components of the pathway, allowing one interaction to pattern subsequent ones. The Notch signal transduction pathway is highly conserved in animal embryogenesis. The REF-1 family of bHLH transcription factors are major targets of Notch signaling in the C. elegans embryo, and are distantly related to HES proteins that are targets of Notch signaling in Drosophila and vertebrates.
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Cell,
2001]
One of the most impressive features of apoptosis is how quickly it all happens. One minute the cell is happily sitting there on its plastic lawn; the next-boom!-it is in convulsions, writhing in its death throes. Many a QuickTime movie has been produced to illustrate this point. Unfortunately, most of these movies stop shortly after the cell falls apart. While less photogenic, what happens to the remains of the cell after the camera stops rolling is no less impressive-at least in vivo.
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Nature Neuroscience,
2004]
At first glance, the nervous systems of vertebrates and invertebrates seem bilaterally symmetrical, but on closer inspection left-right asymmetries become apparent. Humans, for example, show gross anatomical differences between right and left temporal lobes, and visual and language faculties are asymmetrically distributed between the two hemispheres. How these asymmetries arise during development remains something of a mystery (for review, see ref.1). In the nematode Caenorhabditis elegans, the AWC and ASE chemosensory neuron pairs are bilaterally symmetrical based on anatomical considerations, but nevertheless display asymmetrical gene expression patterns. A recent study in nature by Johnston and Hobert identifies a microRNA (miRNA) as a crucial mediator of this asymmetry in the ASE neurons.
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Trends Genet,
2021]
Although many studies have examined quantitative trait variation across many species, only a small number of genes and thereby molecular mechanisms have been discovered. Without these data, we can only speculate about evolutionary processes that underlie trait variation. Here, we review how quantitative and molecular genetics in the nematode Caenorhabditis elegans led to the discovery and validation of 37 quantitative trait genes over the past 15 years. Using these data, we can start to make inferences about evolution from these quantitative trait genes, including the roles that coding versus noncoding variation, gene family expansion, common versus rare variants, pleiotropy, and epistasis play in trait variation across this species.
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Front Genet,
2019]
Onchocerciasis and lymphatic filariasis are targeted for elimination, primarily using mass drug administration at the country and community levels. Elimination of transmission is the onchocerciasis target and global elimination as a public health problem is the end point for lymphatic filariasis. Where program duration, treatment coverage, and compliance are sufficiently high, elimination is achievable for both parasites within defined geographic areas. However, transmission has re-emerged after apparent elimination in some areas, and in others has continued despite years of mass drug treatment. A critical question is whether this re-emergence and/or persistence of transmission is due to persistence of local parasites-i.e., the result of insufficient duration or drug coverage, poor parasite response to the drugs, or inadequate methods of assessment and/or criteria for determining when to stop treatment-or due to re-introduction of parasites <i>via</i> human or vector movement from another endemic area. We review recent genetics-based research exploring these questions in <i>Onchocerca volvulus</i>, the filarial nematode that causes onchocerciasis, and <i>Wuchereria bancrofti</i>, the major pathogen for lymphatic filariasis. We focus in particular on the combination of genomic epidemiology and genome-wide associations to delineate transmission zones and distinguish between local and introduced parasites as the source of resurgence or continuing transmission, and to identify genetic markers associated with parasite response to chemotherapy. Our ultimate goal is to assist elimination efforts by developing easy-to-use tools that incorporate genetic information about transmission and drug response for more effective mass drug distribution, surveillance strategies, and decisions on when to stop interventions to improve sustainability of elimination.
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Methods Cell Biol,
2011]
In Caenorhabditis elegans, newly transcribed RNA is processed in several novel ways. Although introns are removed by a canonical spliceosome, they have evolved several specialized features that reflect the differences in the way they are recognized and the way they are spliced. C. elegans introns are unusually short, in part because they have no specific branch-point sequences and contain minimal polypryimidine tracts. Instead, their 3' splice site is characterized by a highly conserved consensus sequence, which alone may be sufficient to position all spliceosomal elements at the 3' end of the intron. Many RNA molecules are also trans-spliced: a capped 22nt RNA leader is donated by one of a family of specialized snRNPs and spliced to an unpaired 3' splice site, usually just upstream of the start codon. The RNA upstream of this splice site, the outron, is removed during trans-splicing and presumably degraded, making the identification of the transcriptional start site problematic. Transcripts from approximately 70% of all genes are trans-spliced. Trans-splicing has enabled the evolution of operons - multigene clusters in which a single upstream promoter drives the transcription of a polycistronic pre-mRNA. The C. elegans genome contains more than 1000 such operons. The polycistronic pre-mRNA is processed into individual gene-encoding mRNAs by coordinated upstream 3' end formation and downstream trans-splicing. An intercistronic RNA sequence, the Ur element, plays a key role in specifying downstream trans-splicing.
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[
1980]
The practical use of free-living nematodes for aging studies must overcome two problems. Not only must cultures begin with organisms of a similar age, but also reproduction must be prevented, or synchrony will be lost and the aging cultures will become contaminated with newborn orrganisms and will eventually revert to typical "mixed" cultures. The problem of obtaining uniformly small organisms to start cultures has been solved by the use of screens for Turbatrix aceti and the hatching of isolated egg masses for Caenorhabditis elegans. Subsequent reproduction is prevented by the use of the DNA inhibitor fluorodeoxyuridine, or by culturing the organisms at elevated temperatures. Another practical method for aging of T. aceti is the use of a repeated screening process that periodically removes small (young) organisms from the aging cultures.
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Methods Cell Biol,
1995]
DNA transformation assays in a whole organism provide experimental links between molecular structure and phenotype. Experiments with transgenic Caenorhabditis elegans start in general with the injection of DNA into the adult gonad. Effects on phenotype or gene expression patterns can be analyzed either in F1 progeny derived from the injected animals or in derived transgenic lines. Microinjection of C. elegans was first carried out by Kimble et al. (1982). Stinchcomb et al. (1985) then showed that injected DNA could be maintained for several generations in transgenic lines. The first selective methods for producing and maintaining transgenic lines were reported in 1986 (Fire, 1986). These methods have been considerably improved since then (Mello et al., 1991) , so that assays involving DNA transformation are now a standard part of the experimental repertoire for C. elegans.
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Dev Dyn,
2010]
Eukaryotic cells have evolved diverged mechanisms to merge cells. Here, we discuss three types of cell fusion: (1) Non-self-fusion, cells with different genetic contents fuse to start a new organism and fusion between enveloped viruses and host cells; (2) Self-fusion, genetically identical cells fuse to form a multinucleated cell; and (3) Auto-fusion, a single cell fuses with itself by bringing specialized cell membrane domains into contact and transforming itself into a ring-shaped cell. This is a new type of selfish fusion discovered in C. elegans. We divide cell fusion into three stages: (1) Specification of the cell-fusion fate; (2) Cell attraction, attachment, and recognition; (3) Execution of plasma membrane fusion, cytoplasmic mixing and cytoskeletal rearrangements. We analyze cell fusion in diverse biological systems in development and disease emphasizing the mechanistic contributions of C. elegans to the understanding of programmed cell fusion, a genetically encoded pathway to merge specific cells.