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Adv Exp Med Biol,
2013]
Dynamic regulation of histone modifications and small noncoding RNAs is observed throughout the development of the C. elegans germ line. Histone modifications are differentially regulated in the mitotic vs meiotic germ line, on X chromosomes vs autosomes and on paired chromosomes vs unpaired chromosomes. Small RNAs function in transposon silencing and developmental gene regulation. Histone modifications and small RNAs produced in the germ line can be inherited and impact embryonic development. Disruption of histone-modifying enzymes or small RNA machinery in the germ line can result in sterility due to degeneration of the germ line and/or an inability to produce functional gametes.
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Front Cell Dev Biol,
2022]
The proper production of gametes over an extended portion of the life of an organism is essential for a high level of fitness. The balance between germline stem cell (GSC) proliferation (self-renewal) and differentiation (production of gametes) must be tightly regulated to ensure proper gamete production and overall fitness. Therefore, organisms have evolved robust regulatory systems to control this balance. Here we discuss the redundancy in the regulatory system that controls the proliferation vs. differentiation balance in the C. elegans hermaphrodite germline, and how this redundancy may contribute to robustness. We focus on the various types of redundancy utilized to regulate this balance, as well as the approaches that have enabled these redundant mechanisms to be uncovered.
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Epigenetics,
2014]
While most eukaryotic genomes contain transposable elements that can provide select evolutionary advantages to a given organism, failure to tightly control the mobility of such transposable elements can result in compromised genomic integrity of both parental and subsequent generations. Together with the Piwi subfamily of Argonaute proteins, small, non-coding Piwi-interacting RNAs (piRNAs) primarily function in the germ line to defend the genome against the potentially deleterious effects that can be caused by transposition. Here, we describe recent discoveries concerning the biogenesis and function of piRNAs in the nematode Caenorhabditis elegans, illuminating how the faithful production of these mature species can impart a robust defense mechanism for the germ line to counteract problems caused by foreign genetic elements across successive generations by contributing to the epigenetic memory of non-self vs. self.
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Methods Mol Biol,
2006]
One benefit of the nematode Caenorhabditis elegans as a model system is the ease to conduct forward genetic screens and to isolate mutants with phenotypes of interest. However, identifying the mutated genes requires positional cloning, which can be laborious and time consuming. Insertional mutagenesis with a heterologous transposon bypasses the mapping steps and expedites the process of identifying the mutated genes. The Drosophila transposon Mos1 can be mobilized in the C. elegans germline to cause mutations. Mutagenic insertions are subsequently localized within the genome using inverse polymerase chain reaction. The mutagenicity of this technique is roughly one order of magnitude lower than chemical mutagens. However, the molecular identification of the mutated genes is extremely rapid. Therefore, before using Mos1-mediated mutagenesis, one must evaluate the trade-off between time spent screening for mutants vs time spent mapping and rescuing a mutation.
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Int J Environ Res Public Health,
2018]
The receptor for advanced glycation end products (RAGE), a multi-ligand receptor, is mostly associated with promoting inflammation and oxidative stress. In addition to advanced glycation end products (AGEs), its ligands include High mobility group box 1 protein (HMGB-1), S-100 proteins and beta-sheet fibrils. The effects of several metals and metalloids on RAGE expression and activation have been recently studied: in vivo and in vitro exposure to methylmercury, selenium, zinc, manganese, and arsenic was associated with a variety of RAGE-related alterations and behavioral impairments, which are mostly dependent upon the administration procedure (local vs. systemic) and age during exposure. Recently, <i>C. elegans</i> has been proposed as a potential novel model for studying RAGE-related pathologies; preliminary data regarding such model and its potential contribution to the study of metal-induced RAGE-related pathologies are discussed.
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Exp Gerontol,
2006]
Aging is generally defined and studied as a population phenomenon. However, there is great interest, especially when discussing human aging, in the identification of factors that influence the life span of an individual organism. The nematode Caenorhabditis elegans provides an excellent model system for the study of aging at the level of the individual, since young nematodes are essentially clonal yet experience a large range of individual life spans. We are conducting gene expression profiling of individual nematodes, with the aim of discovering genes that vary stochastically in expression between individuals of the same age. Such genes are candidates to modulate the ultimate life span achieved by each individual. We here present statistical analysis of gene expression profiles of individual nematodes from two different microarray platforms, examining the issue of technical vs. biological variance as it pertains to uncovering genes of interest in this paradigm of individual aging.
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Annu Rev Genet,
2008]
Cells split in two at the final step of each division cycle. This division normally bisects through the middle of the cell and generates two equal daughters. However, developmental signals can change the plane of cell cleavage to facilitate asymmetric segregation of fate determinants and control the position and relative sizes of daughter cells. The anaphase spindle instructs the site of cell cleavage in animal cells, hence its position is critical in the regulation of symmetric vs asymmetric cell division. Studies in a variety of models identified evolutionarily conserved mechanisms that control spindle positioning. However, how the spindle determines the cleavage site is poorly understood. Recent results in Caenorhabditis elegans indicate dual functions for a Galpha pathway in positioning the spindle and cleavage furrow.We review asymmetric division of the C. elegans zygote, with a focus on microtubule-cortex interactions that position the spindle and cleavage plane. Expected final online publication date for the Annual Review of Genetics Volume 42 is November 3, 2008. Please see
http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Neurobiol Learn Mem,
2009]
This review surveys the literature that investigates the behavioral characterization and cellular and molecular mechanisms of habituation using the model organism Caenorhabditis elegans. In 1990, C. elegans was first observed to show habituation to a non-localized mechanical tap. The parameters that govern this behavioral plasticity in C. elegans were subsequently characterized, which lead to the important hypothesis that habituation is mediated by multiple mechanisms. Many tools are available to C. elegans researchers that allow for relatively easy genetic manipulation. This has lead to a number of recent genetic studies that have begun to identify key genes and molecules that play a role in the mechanisms of habituation. Some of these genes include a vesicular glutamate transporter, a glutamate receptor subunit, a dopamine receptor and downstream intracellular signaling molecules, such as G proteins and kinases. Some of these genes only affect certain parameters, but not others supporting the hypothesis that multiple mechanisms mediate habituation. The field of research has also led to the dissection of different phases of memory (short-term vs. long-term memory for habituation), which are triggered by different training paradigms. The differences in mechanism between these various forms of memory are also beginning to be revealed.
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J Neurochem,
2018]
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency. This article is protected by copyright. All rights reserved.
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Development,
1990]
Embryonic processes in the nematode C. elegans, the gastropod mollusc Ilyanassa, the dipteran Drosophila, the echinoid Strongylocentrotus purpuratus, the ascidian Ciona, the anuran Xenopus, the teleost Brachydanio and mouse are compared with respect to a series of parameters such as invariant or variable cleavage, the means by which the embryonic axes are set up, egg anisotropies and reliance on conditional or on autonomous specification processes. A molecular interpretation of these modes of specification of cell fate in the embryo is proposed, in terms of spatial modifications of gene regulatory factors. On this basis, classically defined phenomena such as regulative development and cytoplasmic localization can be interpreted at a mechanistic level, and the enormous differences between different forms of embryogenesis in the Animal Kingdom can be considered within a common mechanistic framework. Differential spatial expression of histospecific genes is considered in terms of the structure of the gene regulatory network that will be required in embryos that utilize cell-cell interaction, autonomous vs conditional specification and maternal spatial information to differing extents. It is concluded that the regulatory architectures according to which the programs of gene expression are organized are special to each form of development, and that common regulatory principles are to be found only at lower levels, such as those at which the control regions of histospecific structural genes operate.