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Cell Tissue Res,
2006]
The aim of this review is to introduce the reader to Caenorhabditis elegans as a model system, especially with respect to studies of synapse formation and function. We begin by giving a short description of the structure of the nervous system of C. elegans. As most of the findings that are reviewed here have emerged from studies of neuromuscular junctions (NMJs), two prominent NMJs of C. elegans will be outlined briefly. In addition, we summarize new findings that have added to our understanding of NMJs during the last few years.
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Curr Top Dev Biol,
2005]
"Life is pleasant. Death is peaceful. It''s the transition that''s troublesome," said Isaac Asimov. Indeed, much scientific work over the last hundred years centered around attempts either to stave off or to induce the onset of death, at both the organismal and the cellular levels. In this quest, the nematode C. elegans has proven an invaluable tool, first, in the articulation of the genetic pathway by which programmed cell death proceeds, and also as a continuing source of inspiration. It is our purpose in this Chapter to familiarize the reader with the topic of programmed cell death in C. elegans and its relevance to current research in the fields of apoptosis and cell corpse clearance.
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Genetics,
2016]
The use of next-generation sequencing (NGS) has revolutionized the way phenotypic traits are assigned to genes. In this review, we describe NGS-based methods for mapping a mutation and identifying its molecular identity, with an emphasis on applications in Caenorhabditis elegans In addition to an overview of the general principles and concepts, we discuss the main methods, provide practical and conceptual pointers, and guide the reader in the types of bioinformatics analyses that are required. Owing to the speed and the plummeting costs of NGS-based methods, mapping and cloning a mutation of interest has become straightforward, quick, and relatively easy. Removing this bottleneck previously associated with forward genetic screens has significantly advanced the use of genetics to probe fundamental biological processes in an unbiased manner.
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Worm,
2013]
The development of next-generation sequencing technologies has enabled rapid and cost effective whole genome sequencing. This technology has allowed researchers to shortcut time-consuming and laborious methods used to identify nucleotide mutations in forward genetic screens in model organisms. However, causal mutations must still be mapped to a region of the genome so as to aid in their identification. This can be achieved simultaneously with deep sequencing through various methods. Here we discuss alternative deep sequencing strategies for simultaneously mapping and identifying causal mutations in Caenorhabditis elegans from mutagenesis screens. Focusing on practical considerations, such as the particular mutant phenotype obtained, this review aims to aid the reader in choosing which strategy to adopt to successfully clone their mutant.
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Genesis,
2011]
Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.
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Front Cell Dev Biol,
2020]
In most eukaryotes, the genome is packaged with histones and other proteins to form chromatin. One of the major mechanisms for chromatin regulation is through post-translational modification of histone proteins. Recognition of these modifications by effector proteins, often dubbed histone "readers," provides a link between the chromatin landscape and gene regulation. The diversity of histone reader proteins for each modification provides an added layer of regulatory complexity. In this review, we will focus on the roles of chromatin organization modifier (chromo) domain containing proteins in the model nematode, <i>Caenorhabditis elegans</i>. An amenability to genetic and cell biological approaches, well-studied development and a short life cycle make <i>C. elegans</i> a powerful system to investigate the diversity of chromo domain protein functions in metazoans. We will highlight recent insights into the roles of chromo domain proteins in the regulation of heterochromatin and the spatial conformation of the genome as well as their functions in cell fate, fertility, small RNA pathways and transgenerational epigenetic inheritance. The spectrum of different chromatin readers may represent a layer of regulation that integrates chromatin landscape, genome organization and gene expression.
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Mech Ageing Dev,
2016]
Drugs screenings in search of enhancer or suppressors of selected readout(s) are nowadays mainly carried out in single cells systems. These approaches are however limited when searching for compounds with effects at the organismal level. To overcome this drawback the use of different model organisms to carry out modifier screening has exponentially grown in the past decade. Unique characteristics such as easy manageability, low cost, fast reproductive cycle, short lifespan, simple anatomy and genetic amenability, make the nematode Caenorhabditis elegans especially suitable for this purpose. Here we briefly review the different high-throughput and high-content screenings which exploited the nematode to identify new compounds extending healthy lifespan. In this context, we describe our recently developed screening strategy to search for pro-longevity interventions taking advantage of the very reproducible phenotypes observed in C. elegans upon different degrees of mitochondrial stress. Indeed, in Mitochondrial mutants, the processes induced to cope with mild mitochondrial alterations during development, and ultimately extending animal lifespan, lead to reduced size and induction of specific stress responses. Instead, upon strong mitochondrial dysfunction, worms arrest their development. Exploiting these automatically quantifiable phenotypic readouts, we developed a new screening approach using the Cellomics ArrayScanVTI-HCS Reader and identified a new pro-longevity drug.
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Annu Rev Genet,
1994]
All metazoans possess extracellular matrices (ECM) composed of complex assemblies of molecules with generally well conserved structures and functions. ECM play structural roles, providing scaffolds that organize and strengthen tissues, and instructional roles, influencing differentiation and development. Major ECM components include the collagens, a diverse family of fibrous proteins distinguished by their triple-helical coiled coil structure, other large glycoproteins, such as laminin, fibronectin and nidogen, and proteoglycans, proteins with attached glycosaminoglycan chains. For most ECM components, cell surface receptors have been identified that can mediate interactions between the cell and its ECM. The nematode Caenorhabditis elegans is an excellent system for studies of the structures and functions of ECM components, and their roles in development. C. elegans is the simplest metazoan in which detailed genetic analysis of the ECM can be performed. The complete cell lineage and detailed anatomical structure of the organism have been described. The simple life style of C. elegans allows animals with severe morphological and/or motility defects to survive and, because they are internally self-fertilizing hermaphrodites, even reproduce. These properties can simplify mutational analyses of genes encoding ECM components. Two major forms of ECM have been identified in C. elegans, the cuticle and basement membranes. The cuticle, or exoskeleton, covers the outside of the animal and lines the lumen of the pharynx. Basement membranes cover the pseudocoelomic faces of the pharynx, intestine, gonad, and hypodermis. There is no visible interstitial matrix between the cells within tissues, possibly because nearly all cells are adjacent to the cuticle or a basement membrane. This review focuses on studies of the ECM in C. elegans. The reader is referred to excellent recent reviews concerning related topics: collagens in other nematodes; mutations in human fibrillar collagens; mutations in human type IV collagen; composition