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Curr Opin Genet Dev,
2012]
The identity of individual cell types in a multicellular organism appears to be continuously maintained through active processes but is not irreversible. Changes in the identity of individual cell types can be brought about through ectopic mis-expression of regulatory factors, but in a number of cases also occurs in normal development. I will review here these natural cellular reprogramming processes occurring in the invertebrate model organisms Caenorhabditis elegans and Drosophila melanogaster. Furthermore, I will discuss the issue of why only certain cell types can be converted during induced reprogramming processes evoked by ectopic expression of regulatory factors and how recent work in model systems have shown that this cellular context-dependency can be manipulated.
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Front Neurosci,
2021]
Cell fate conversion by the forced overexpression of transcription factors (TFs) is a process known as reprogramming. It leads to de-differentiation or <i>trans-</i>differentiation of mature cells, which could then be used for regenerative medicine applications to replenish patients suffering from, e.g., neurodegenerative diseases, with healthy neurons. However, TF-induced reprogramming is often restricted due to cell fate safeguarding mechanisms, which require a better understanding to increase reprogramming efficiency and achieve higher fidelity. The germline of the nematode <i>Caenorhabditis elegans</i> has been a powerful model to investigate the impediments of generating neurons from germ cells by reprogramming. A number of conserved factors have been identified that act as a barrier for TF-induced direct reprogramming of germ cells to neurons. In this review, we will first summarize our current knowledge regarding cell fate safeguarding mechanisms in the germline. Then, we will focus on the molecular mechanisms underlying neuronal induction from germ cells upon TF-mediated reprogramming. We will shortly discuss the specific characteristics that might make germ cells especially fit to change cellular fate and become neurons. For future perspectives, we will look at the potential of <i>C. elegans</i> research in advancing our knowledge of the mechanisms that regulate cellular identity, and what implications this has for therapeutic approaches such as regenerative medicine.
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J Dev Biol,
2020]
The potential of a cell to produce all types of differentiated cells in an organism is termed totipotency. Totipotency is an essential property of germ cells, which constitute the germline and pass on the parental genetic material to the progeny. The potential of germ cells to give rise to a whole organism has been the subject of intense research for decades and remains important in order to better understand the molecular mechanisms underlying totipotency. A better understanding of the principles of totipotency in germ cells could also help to generate this potential in somatic cell lineages. Strategies such as transcription factor-mediated reprogramming of differentiated cells to stem cell-like states could benefit from this knowledge. Ensuring pluripotency or even totipotency of reprogrammed stem cells are critical improvements for future regenerative medicine applications. The <i>C. elegans</i> germline provides a unique possibility to study molecular mechanisms that maintain totipotency and the germ cell fate with its unique property of giving rise to meiotic cells Studies that focused on these aspects led to the identification of prominent chromatin-repressing factors such as the <i>C. elegans</i> members of the Polycomb Repressive Complex 2 (PRC2). In this review, we summarize different factors that were recently identified, which use molecular mechanisms such as control of protein translation or chromatin repression to ensure maintenance of totipotency and the germline fate. Additionally, we focus on recently identified factors involved in preventing transcription-factor-mediated conversion of germ cells to somatic lineages. These so-called reprogramming barriers have been shown in some instances to be conserved with regard to their function as a cell fate safeguarding factor in mammals. Overall, continued studies assessing the different aspects of molecular pathways involved in maintaining the germ cell fate in <i>C. elegans</i> may provide more insight into cell fate safeguarding mechanisms also in other species.
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Curr Biol,
2005]
Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode''''s Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during
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Genetics,
2019]
The <b>T</b>arget <b>o</b>f <b>R</b>apamycin (TOR or mTOR) is a serine/threonine kinase that regulates growth, development, and behaviors by modulating protein synthesis, autophagy, and multiple other cellular processes in response to changes in nutrients and other cues. Over recent years, TOR has been studied intensively in mammalian cell culture and genetic systems because of its importance in growth, metabolism, cancer, and aging. Through its advantages for unbiased, and high-throughput, genetic and <i>in vivo</i> studies, <i>Caenorhabditis elegans</i> has made major contributions to our understanding of TOR biology. Genetic analyses in the worm have revealed unexpected aspects of TOR functions and regulation, and have the potential to further expand our understanding of how growth and metabolic regulation influence development. In the aging field, <i>C. elegans</i> has played a leading role in revealing the promise of TOR inhibition as a strategy for extending life span, and identifying mechanisms that function upstream and downstream of TOR to influence aging. Here, we review the state of the TOR field in <i>C. elegans</i>, and focus on what we have learned about its functions in development, metabolism, and aging. We discuss knowledge gaps, including the potential pitfalls in translating findings back and forth across organisms, but also describe how TOR is important for <i>C. elegans</i> biology, and how <i>C. elegans</i> work has developed paradigms of great importance for the broader TOR field.
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Trends in Cell Biology,
1996]
Cellular microtubules assemble and disassemble at a variety of rates and frequencies, and these properties contribute directly to the cell-cycle-associated rearrangements of the microtubule cytoskeleton and to the molecular basis of mitosis. The kinetics of assembly/disassembly are governed, in part, by the hydrolysis of GTP bound to the B-tubulin nucleotide-binding site. The B-tubulin GTP-binding site, therefore, lies at the heart of microtubule assembly-disassembly kinetics, and the elucidation of its structure is central to an understanding of the cellular behaviour of microtubules. Unfortunately, the crystallographic structure of B-tubulin is not yet available. In this review, we describe the progress being made using mutagenesis and biochemical studies to understand the structure of this unusual GTP-binding site.
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Microbiol Mol Biol Rev,
2021]
SUMMARYExtensive use of chemical insecticides adversely affects both environment and human health. One of the most popular biological pest control alternatives is bioinsecticides based on <i>Bacillus thuringiensis</i> This entomopathogenic bacterium produces different protein types which are toxic to several insect, mite, and nematode species. Currently, insecticidal proteins belonging to the Cry and Vip3 groups are widely used to control insect pests both in formulated sprays and in transgenic crops. However, the benefits of <i>B. thuringiensis</i>-based products are threatened by insect resistance evolution. Numerous studies have highlighted that mutations in genes coding for surrogate receptors are responsible for conferring resistance to <i>B. thuringiensis</i> Nevertheless, other mechanisms may also contribute to the reduction of the effectiveness of <i>B. thuringiensis</i>-based products for managing insect pests and even to the acquisition of resistance. Here, we review the relevant literature reporting how invertebrates (mainly insects and <i>Caenorhabditis elegans</i>) respond to exposure to <i>B. thuringiensis</i> as either whole bacteria, spores, and/or its pesticidal proteins.
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1986]
Wild-type body wall muscle cells of Caenorhabditis elegans produce at a constant ratio two myosin heavy chain isoforms, A and B, that form homodimeric myosins. Electron microscopy of negatively stained complexes of isoform-specific antibodies with isolated thick filaments shows that the surface of the 9.7 =B5m long filament is differentiated with respect to myosin content: a medial 1.8 =B5m zone contains myosin A and two polar 4.4 = =B5m zones contain myosin B. Biochemical and electron microscopic studies show that at 0.45 M KC1, pH 6.35, myosin B and paramyosin are solubilized. The medial all-myosin A region with novel core structures extending in a polar manner remain. These dissociation experiments suggest a sequential model for wild-type thick filament assembly in which myosins A and B would participate in the initiation and termination of assembly, respectively. Analysis of mutant thick filaments clarifies the relationship of the myosin isoforms. CB190 (
unc-54 I) thick filaments contain myosin A only and have normal length. CB1214 (
unc-15 I) mutants produce no paramyosin, and their thick filaments are composed of a medial myosin region
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Results Probl Cell Differ,
2017]
Asymmetric cell division is a common mode of cell differentiation during the invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage, and continuing throughout embryogenesis and larval development, mother cells are polarized by Wnt ligands, causing an asymmetric inheritance of key members of a Wnt/B-catenin signal transduction pathway termed the Wnt/B-catenin asymmetry pathway. The resulting daughter cells are distinct at birth with one daughter cell activating Wnt target gene expression via B-catenin activation of TCF, while the other daughter displays transcriptional repression of these target genes. Here, we seek to review the body of evidence underlying a unified model for Wnt-driven asymmetric cell division in C. elegans, identify global themes that occur during asymmetric cell division, as well as highlight tissue-specific variations. We also discuss outstanding questions that remain unanswered regarding this intriguing mode of asymmetric cell division.
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Ciba Found Symp,
1987]
Human lymphatic filariasis is caused mainly by Wuchereria bancrofti, Brugia malayi and Brugia timori. Of the estimated 90.2 million people infected, more than 90% have bancroftian and less than 10% brugian filariasis. The distribution and transmission of the disease are closely associated with socioeconomic and behavioural factors in endemic populations. Urban W. bancrofti infection, as seen in South-East Asia, is related to poor urban sanitation, which leads to intense breeding of Culex quiquefasciatus, the principal vector. Rural strains of W. bancrofti are transmitted primarily by Anopheles spp. and Aedes spp. mosquitoes. Brugian filariasis is mainly a rural disease transmitted by Mansonia, Anopheles and Aedes spp. mosquitoes. The periodic form of B. malayi is principally a human parasite, whereas the subperiodic form is zoonotically transmitted in some countries. The control of filariasis has relied on chemotherapy, vector control and reduction of human-vector contact. Although eradication of W. bancrofti and periodic B. malayi can be achieved, it is possible only to reduce transmission of zoonotic subperiodic B. malayi in some areas. A rational approach to control should consider ecological, socioeconomic and behavioural factors and, where feasible, integrate control programmes into the delivery system for primary health care.