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Genome Res,
2000]
Whole -genome sequence comparisons between bacterial sequences are one thing, but try comparing two eukaryotic genomes, each containing tens or hundreds of millions of nucleotides. And try to do it on your desktop machine in your office or at home. That is what Kent and Zahler have tried, and the results are presented in this issue of Genome Research. The use of evolutionary conservation to unveil functional information contained within genomes is not new. In the case of the nematode, comparisons of Caenorhabditis elegans to its close relative Caenorhabditis briggsae go back as far as Emmons et al.
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Traffic,
2019]
Bonafide claudin proteins are functional and structural components of tight junctions and are largely responsible for barrier formation across epithelial and endothelial membranes. However, current advances in the understanding of claudin biology have revealed their unexpected functions in the brain. Apart from maintaining blood-brain barriers in the brain, other functions of claudins in neurons and at synapses have been largely elusive and are just coming to light. In this review, we summarize the functions of claudins in the brain and their association in neuronal diseases. Further, we go on to cover some recent studies that show that claudins play signaling functions in neurons by regulating trafficking of postsynaptic receptors and controlling dendritic morphogenesis in the model organism Caenorhabditis elegans. This article is protected by copyright. All rights reserved.
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F1000Res,
2018]
Establishing and maintaining cell polarity are dynamic processes that necessitate complicated but highly regulated protein interactions. Phosphorylation is a powerful mechanism for cells to control the function and subcellular localization of a target protein, and multiple kinases have played critical roles in cell polarity. Among them, atypical protein kinase C (aPKC) is likely the most studied kinase in cell polarity and has the largest number of downstream substrates characterized so far. More than half of the polarity proteins that are essential for regulating cell polarity have been identified as aPKC substrates. This review covers mainly studies of aPKC in regulating anterior-posterior polarity in the worm one-cell embryo and apical-basal polarity in epithelial cells and asymmetrically dividing cells (for example, <i>Drosophila</i> neuroblasts). We will go through aPKC target proteins in cell polarity and discuss various mechanisms by which aPKC phosphorylation controls their subcellular localizations and biological functions. We will also review the recent progress in determining the detailed molecular mechanisms in spatial and temporal control of aPKC subcellular localization and kinase activity during cell polarization.
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Mol Reprod Dev,
2010]
Germ cells occupy a unique position in animal reproduction, development, and evolution. In sexually reproducing animals, only they can produce gametes and contribute genetically to subsequent generations. Nonetheless, germ line specification during embryogenesis is conceptually the same as the specification of any somatic cell type: germ cells must activate a specific gene regulatory network in order to differentiate and go through gametogenesis. While many genes with critical roles in the germ line have been characterized with respect to expression pattern and genetic interactions, it is the molecular interactions of the relevant gene products that are ultimately responsible for germ cell differentiation. This review summarizes the current state of knowledge on the molecular functions and biochemical connections between germ line gene products. We find that homologous genes often interact physically with the same conserved molecular partners across the metazoans. We also point out cases of nonhomologous genes from different species whose gene products play analogous biological roles in the germ line. We suggest a preliminary molecular definition of an ancestral "pluripotency module" that could have been modified during metazoan evolution to become specific to the germ line.
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Mol Cell Neurosci,
2020]
Cell polarity is defined as the asymmetric distribution of cellular components along an axis. Most cells, from the simplest single-cell organisms to highly specialized mammalian cells, are polarized and use similar mechanisms to generate and maintain polarity. Cell polarity is important for cells to migrate, form tissues, and coordinate activities. During development of the mammalian cerebral cortex, cell polarity is essential for neurogenesis and for the migration of newborn but as-yet undifferentiated neurons. These oriented migrations include both the radial migration of excitatory projection neurons and the tangential migration of inhibitory interneurons. In this review, I will first describe the development of the cerebral cortex, as revealed at the cellular level. I will then define the core molecular mechanisms - the Par/Crb/Scrib polarity complexes, small GTPases, the actin and microtubule cytoskeletons, and phosphoinositides/PI3K signaling - that are required for asymmetric cell division, apico-basal and front-rear polarity in model systems, including C elegans zygote, Drosophila embryos and cultured mammalian cells. As I go through each core mechanism I will explain what is known about its importance in radial and tangential migration in the developing mammalian cerebral cortex.
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WormBook,
2015]
A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) Caenorhabditis elegans as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on C. elegans has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host-parasite interactions, and evolution. C. elegans has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in C. elegans research. Key to studying C. elegans has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make C. elegans useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues.
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Cytometry A,
2011]
Small multicellular organisms such as nematodes, fruit flies, clawed frogs, and zebrafish are emerging models for an increasing number of biomedical and environmental studies. They offer substantial advantages over cell lines and isolated tissues, providing analysis under normal physiological milieu of the whole organism. Many bioassays performed on these alternative animal models mirror with a high level of accuracy those performed on inherently low-throughput, costly, and ethically controversial mammalian models of human disease. Analysis of small model organisms in a high-throughput and high-content manner is, however, still a challenging task not easily susceptible to laboratory automation. In this context, recent advances in photonics, electronics, as well as material sciences have facilitated the emergence of miniaturized bioanalytical systems collectively known as Lab-on-a-Chip (LOC). These technologies combine micro- and nanoscale sciences, allowing the application of laminar fluid flow at ultralow volumes in spatially confined chip-based circuitry. LOC technologies are particularly advantageous for the development of a wide array of automated functionalities. The present work outlines the development of innovative miniaturized chip-based devices for the in situ analysis of small model organisms. We also introduce a new term "wormometry" to collectively distinguish these up-and-coming chip-based technologies that go far beyond the conventional meaning of the term "cytometry."
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Genetics,
2022]
Light microscopes are the cell and developmental biologists' "best friend", providing a means to see structures and follow dynamics from the protein to the organism level. A huge advantage of C. elegans as a model organism is its transparency, which coupled with its small size means that nearly every biological process can be observed and measured with the appropriate probe and light microscope. Continuous improvement in microscope technologies along with novel genome editing techniques to create transgenic probes have facilitated the development and implementation of a dizzying array of methods for imaging worm embryos, larvae and adults. In this review we provide an overview of the molecular and cellular processes that can be visualized in living worms using light microscopy. A partial inventory of fluorescent probes and techniques successfully used in worms to image the dynamics of cells, organelles, DNA, and protein localization and activity is followed by a practical guide to choosing between various imaging modalities, including widefield, confocal, lightsheet, and structured illumination microscopy. Finally, we discuss the available tools and approaches, including machine learning, for quantitative image analysis tasks, such as colocalization, segmentation, object tracking, and lineage tracing. Hopefully, this review will inspire worm researchers who have not yet imaged their worms to begin, and push those who are imaging to go faster, finer, and longer.
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Exp Neurobiol,
2022]
Patients suffering from rare human diseases often go through a painful journey for finding a definite molecular diagnosis prerequisite of appropriate cures. With a novel variant isolated from a single patient, determination of its pathogenicity to end such "diagnostic odyssey" requires multi-step processes involving experts in diverse areas of interest, including clinicians, bioinformaticians and research scientists. Recent efforts in building large-scale genomic databases and <i>in silico</i> prediction platforms have facilitated identification of potentially pathogenic variants causative of rare human diseases of a Mendelian basis. However, the functional significance of individual variants remains elusive in many cases, thus requiring incorporation of versatile and rapid model organism (MO)-based platforms for functional analyses. In this review, the current scope of rare disease research is briefly discussed. In addition, an overview of invertebrate MOs for their key features relevant to rare neurological diseases is provided, with the characteristics of two representative invertebrate MOs, <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>, as well as the challenges against them. Finally, recently developed research networks integrating these MOs in collaborative research are portraited with an array of bioinformatical analyses embedded. A comprehensive survey of MO-based research activities provided in this review will help us to design a wellstructured analysis of candidate genes or potentially pathogenic variants for their roles in rare neurological diseases in future.
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Parasitol Today,
1992]
Like particle physics, biology is now a big expensive business, and like CERN, the genome projects alternately provoke admiration and detraction. Some feel that it would be more valuable to go for specific genes of interest rather than fill databases with sequences of junk DNA. The detractors would also say that the costs entailed, the limited intellectual and practical payback, and the ethical worries are too big to justify. But like the mythological juggernaut, once started it won't stop and it is indisputable that exciting information will come out of these efforts. Like some of the best discoveries many will be unexpected and have repercussions of immense value. This is indisputable on statistical grounds alone; the Caenorhabditis elegans genome is estimated to contain tens of thousands of genes. However, genome projects cannot be justified by serendipity and they do have obvious immediate value for tracing the genes involved in cancer and other inheritable disorders, and indeed for the multiple technological spin-offs. The C. elegans genome project is already bearing luscious fruit, of the 34 genes reported so far some of which have sequence similarity with genes such as glutathione reductase, an immunogenic protein from Trichostrongylus colubriformis, acetyl-CoA acetyltransferase and various other enzymes, growth factors and signal transducing components. Up-to-date cDNA data will be published by John Sulston and his colleagues in the early issues of Nature Genetics, due out this month.