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Curr Biol,
2004]
Gonad morphogenesis in Caenorhabditis elegans requires two secreted proteases. Recent studies show that alterations of the extracellular matrix component fibulin-1 rescue gonadogenesis in the absence of these proteases. This finding is a critical step toward understanding the role of extracellular matrix in organogenesis.
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Curr Biol,
2005]
Axon pruning has recently been described in the simple nervous system of the nematode Caenorhabditis elegans. Generating excess processes and pruning may be a phylogenetically conserved feature reflecting a flexibility to modify neural circuits.
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Front Endocrinol (Lausanne),
2016]
Steroid hormones regulate physiological processes in species ranging from plants to humans. A wide range of steroid hormones exist, and their contributions to processes, such as growth, reproduction, development, and aging, is almost always complex. Understanding the biosynthetic pathways that generate steroid hormones and the signaling pathways that mediate their effects is thus of fundamental importance. In this work, we review recent advances in (i) the biological role of steroid hormones in the roundworm Caenorhabditis elegans and (ii) the development of novel methods to facilitate the detection and identification of these molecules. Our current understanding of steroid signaling in this simple organism serves to illustrate the challenges we face moving forward. First, it seems clear that we have not yet identified all of the enzymes responsible for steroid biosynthesis and/or degradation. Second, perturbation of steroid signaling affects a wide range of phenotypes, and subtly different steroid molecules can have distinct effects. Finally, steroid hormone levels are critically important, and minute variations in quantity can profoundly impact a phenotype. Thus, it is imperative that we develop innovative analytical tools and combine them with cutting-edge approaches including comprehensive and highly selective liquid chromatography coupled to mass spectrometry based on new methods such as supercritical fluid chromatography coupled to mass spectrometry (SFC-MS) if we are to obtain a better understanding of the biological functions of steroid signaling.
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1976]
The isolation of behavioural mutants of an organism can provide a variety of strains that are somehow altered in normal neural function. By physiological, anatomical, and biochemical analysis of such alterations it should be possible to correlate the behavioural defect with an underlying neurological defect. From such correlations, the functional role of the defective elements of the nervous system can be deduced. For such analysis the mutations can be thought of as a dissecting tool used to cut parts of the nervous system to determine the behavioural consequences of such cuts. Pursuit of the underlying defects in behavioural mutants leads rapidly beyond just the analysis of neural function. One is let to ask what kinds of cuts are made by the genetic dissecting tool? What alterations in a nervous system can be introduced by single gene mutations? How did the defective gene product cause such an alteration? Such questions about the genetic specification of the development of the nervous system may also be approached by the study of behavioural mutants. In this chapter, I will first illustrate some of the ways that behavioural mutants of Caenorhabditis elegans can be used to study the function of the sensory nervous sytem and then show how the anatomical analysis of such mutants leads to questions about neural
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J Chromatogr B Analyt Technol Biomed Life Sci,
2003]
Whole genome sequencing of the free-living nematode Caenorhabditis elegans is a prominent achievement in genomics and uncovers the existence of enormous known and unknown gene products. Characterization and linking of all gene products are the next challenging theme of biology. Genome-wide researches are already progressing on C. elegans and the fruits of these efforts are accessible through the internet. To link the sequence-function relationship, proteomic research has been applied to provide comprehensive information of the worm proteins. In addition to 2-dimensional gel electrophoresis for visualization of the proteome, recent advances in liquid chromatography (LC)-based technologies have allowed the large-scale analysis of proteins and are at cutting-edge of high-throughput analysis of focused proteome.
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Semin Cell Dev Biol,
2023]
Programmed cell death (PCD) is crucial for normal development and homeostasis. Our first insights into the genetic regulation of apoptotic cell death came from in vivo studies in the powerful genetic model system of C. elegans. More recently, novel developmental cell death programs occurring both embryonically and post-embryonically, and sex-specifically, have been elucidated. Recent studies in the apoptotic setting have also shed new light on the intricacies of phagocytosis in particular. This review provides a brief historical perspective of the origins of PCD studies in C. elegans, followed by a more detailed description of non-canonical apoptotic and non-apoptotic death programs. We conclude by posing open questions and commenting on our outlook on the future of PCD studies in C. elegans, highlighting the importance of advanced imaging tools and the continued leveraging of C. elegans genetics both with classical and modern cutting-edge approaches.
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Human Molecular Genetics,
2004]
Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messenger RNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation. Advances in targeted delivery of RNAi-inducing molecules has raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology and we address problems to be solved in developing RNAi-based therapies.
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Genetica,
2009]
The nematode Caenorhabditis elegans is a widely appreciated, powerful platform in which to study important biological mechanisms related to human health. More than 65% of human disease genes have homologues in the C. elegans genome, and essential aspects of mammalian cell biology, neurobiology and development are faithfully recapitulated in this organism. The EU-funded NemaGENETAG project was initiated with the aim to develop cutting-edge tools and resources that will facilitate modelling of human pathologies in C. elegans, and advance our understanding of animal development and physiology. The main objective of the project involves the generation and evaluation of a large collection of transposon-tagged mutants. In the process of achieving this objective the NemaGENETAG consortium also endeavours to optimize and automate existing transposon-mediated mutagenesis methodologies based on the Mos1 transposable element, in addition to developing alternatives using other transposon systems. The final product of this initiative-a comprehensive collection of transposon-tagged alleles-together with the acquisition of efficient transposon-based tools for mutagenesis and transgenesis in C. elegans, should yield a wealth of information on gene function, immediately relevant to key biological processes and to pharmaceutical research and development.
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Semin Cell Dev Biol,
2014]
In the nematode C. elegans, both males and self-fertile hermaphrodites produce sperm. As a result, researchers have been able to use a broad range of genetic and genomic techniques to dissect all aspects of sperm development and function. Their results show that the early stages of spermatogenesis are controlled by transcriptional and translational processes, but later stages are dominated by protein kinases and phosphatases. Once spermatids are produced, they participate in many interactions with other cells - signals from the somatic gonad determine when sperm activate and begin to crawl, signals from the female reproductive tissues guide the sperm, and signals from sperm stimulate oocytes to mature and be ovulated. The sperm also show strong competitive interactions with other sperm and oocytes. Some of the molecules that mediate these processes have conserved functions in animal sperm, others are conserved proteins that have been adapted for new roles in nematode sperm, and some are novel proteins that provide insights into evolutionary change. The advent of new techniques should keep this system on the cutting edge of research in cellular and reproductive biology.
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Biol Chem,
2010]
Depending on their chemical structure and properties, environmental chemicals and other xenobiotics that enter the cell can affect cellular function by either nonselective binding to cellular macromolecules or by interference with cellular receptors, which would initiate a more defined cell biological response. One of these intracellular chemosensor molecules is the aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family that is known to mediate the biochemical and toxic effects of dioxins, polyaromatic hydrocarbons and related compounds. Numerous investigations have revealed that the AhR is not only a master regulator of drug metabolism activated by anthropogenic chemicals, but is also triggered by natural and endogenous ligands and can influence cell biological endpoints such as growth and differentiation. Cutting-edge research has identified new intriguing functions of the AhR, such as during proteasomal degradation of steroid hormone receptors, the cellular UVB stress response and the differentiation of certain T-cell subsets. In this review we provide both a survey of the fundamental basics of AhR biology and an insight into new functional aspects of AhR signaling to further stimulate research on this intriguing transcription factor at the interface between toxicology, cell biology and immunology.