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Apoptosis,
2014]
The death associated protein kinases (DAPK) are a phylogenetically widespread family of calcium-regulated serine/threonine kinases, initially identified from their roles in apoptosis. Subsequent studies, principally in vertebrate cells or models, have elucidated the functions of the DAPK family in autophagy and tumor suppression. Invertebrate genetic model organisms such as Drosophila and C. elegans have revealed additional functions for DAPK and related kinases. In the nematode C. elegans, the sole DAPK family member DAPK-1 positively regulates starvation-induced autophagy. Genetic analysis in C. elegans has revealed that DAPK-1 also acts as a negative regulator of epithelial innate immune responses in the epidermis. This negative regulatory role for DAPK in innate immunity may be analogous to the roles of mammalian DAPK in inflammatory responses.
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Microorganisms,
2020]
The bacterivorous nematode <i>Caenorhabditis elegans</i> is an important model species for understanding genetic variation of complex traits. So far, most studies involve axenic laboratory settings using <i>Escherichia coli</i> as the sole bacterial species. Over the past decade, however, investigations into the genetic variation of responses to pathogenic microbiota have increasingly received attention. Quantitative genetic analyses have revealed detailed insight into loci, genetic variants, and pathways in <i>C. elegans</i> underlying interactions with bacteria, microsporidia, and viruses. As various quantitative genetic platforms and resources like <i>C. elegans</i> Natural Diversity Resource (CeNDR) and Worm Quantitative Trait Loci (WormQTL) have been developed, we anticipate that expanding <i>C. elegans</i> research along the lines of genetic variation will be a treasure trove for opening up new insights into genetic pathways and gene functionality of microbiota interactions.
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Nucleus,
2015]
The nuclear envelope consists of 2 membranes separated by 30-50 nm, but how the 2 membranes are evenly spaced has been an open question in the field. Nuclear envelope bridges composed of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins have been proposed to set and regulate nuclear envelope spacing. We tested this hypothesis directly by examining nuclear envelope spacing in Caenorhabditis elegans animals lacking UNC-84, the sole somatic SUN protein. SUN/KASH bridges are not required to maintain even nuclear envelope spacing in most tissues. However, UNC-84 is required for even spacing in body wall muscle nuclei. Shortening UNC-84 by 300 amino acids did not narrow the nuclear envelope space. While SUN proteins may play a role in maintaining nuclear envelope spacing in cells experiencing forces, our data suggest they are dispensable in most cells.
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J Biosci Bioeng,
2013]
The field of metabolomics continues to grow rapidly over the last decade and has been proven to be a powerful technology in predicting and explaining complex phenotypes in diverse biological systems. Metabolomics complements other omics, such as transcriptomics and proteomics and since it is a 'downstream' result of gene expression, changes in the metabolome is considered to best reflect the activities of the cell at a functional level. Thus far, metabolomics might be the sole technology capable of detecting complex, biologically essential changes. As one of the omics technology, metabolomics has exciting applications in varied fields, including medical science, synthetic biology, medicine, and predictive modeling of plant, animal and microbial systems. In addition, integrated applications with genomics, transcriptomics, and proteomics provide greater understanding of global system biology. In this review, we discuss recent applications of metabolomics in microbiology, plant, animal, food, and medical science.
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Front Biosci,
2004]
In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway controls a cell migration whereas noncanonical Wnt pathways control the polarities of individual cells. Despite the differences in the identities and interactions among canonical and noncanonical Wnt pathway components, as well as the processes they regulate, almost all C. elegans Wnt pathways involve the sole Tcf homolog, POP-1. Intriguingly, POP-1 is asymmetrically distributed between the daughters of an asymmetric cell division, with the anterior sister cell usually having a higher level of nuclear POP-1 than its posterior sister. At some divisions, asymmetric distribution of POP-1 is controlled by noncanonical Wnt signaling, but at others the asymmetry is generated independently. Recent experiments suggest that despite this elaborate anterior-posterior POP-1 asymmetry, the quantity of POP-1 protein may have less to do with the subsequent determination of fate than does the quality of the POP-1 protein in the cell. In this review, we will embark on a quest to understand Quality (1), at least from the standpoint of the effect POP/Tcf quality has on the control of cell polarity in C. elegans.
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Cell Death Differ,
2009]
Lethal mitochondrial membrane permeabilization has been depicted as the result of two fundamentally distinct processes, namely primary mitochondrial outer membrane permeabilization (MOMP) versus permeability transition (PT) ignited at the level of the mitochondrial inner membrane. MOMP and PT have been connected to apoptosis and necrosis, respectively. Moreover, it has been thought that MOMP was mediated by pro-apoptotic multidomain proteins of the Bcl-2 family (Bax and Bak), which would operate near-to-independently from the permeability transition pore complex (PTPC) composed by voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT) and cyclophilin D. A recent paper in Molecular and Cellular Biology now reveals the obligate contribution of one particular ANT isoform to the execution of developmental and homeostatic cell death in Caenorhabditis elegans. The physical and functional interaction between CED-9, the sole multidomain Bcl-2 protein of C. elegans, and ANT emphasizes the existence of an intricate, phylogenetically conserved crosstalk between Bcl-2 family proteins and constituents of the PTPC. In this issue of Cell Death and Differentiation, Malorni et al. further corroborate this notion by showing that type 2 transglutaminase (TG2) is essential for the correct assembly/function of ANT1, and that, at least in some experimental settings, TG2 might be required to enable and/or stabilize the pro-apoptotic association of Bax with ANT1.
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Curr Top Dev Biol,
2015]
In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early development until the onset of gastrulation at approximately the 28-cell stage takes place normally even in the absence of zygotic transcription. Therefore, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs, respectively, that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation. Protein phosphorylation is extensively used throughout the C. elegans maternal-to-zygotic transition (MZT): (1) for maternal protein activation, (2) for coordination of the meiotic and mitotic cell cycle, (3) to mark specific proteins for degradation, and/or (4) to switch the biochemical activity of specific proteins. Maternally loaded mRNAs are regulated primarily by a set of maternal RNA-binding proteins (RBPs), each of which binds to sometimes overlapping target sequences within the mRNA 3'UTRs and either promotes or inhibits translation. Most maternal transcripts are uniformly distributed throughout the embryo but specific transcripts are translated only in certain blastomeres. This control is achieved by the asymmetric distribution of the maternal RBPs, such that the blastomere-specific constellation of RBPs present, and their relative levels, determines the translational readout for their target transcripts. In certain well-studied cases, such as the specification of the sole endodermal precursor in the 8-cell embryo, the maternal transcripts and proteins along with their directly targeted zygotic genes have been identified.
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WormBook,
2006]
There are two sexes in C. elegans, hermaphrodite and male. While there are many sex-specific differences between males and hermaphrodites that affect most tissues, the basic body plan and many of its structures are identical. However, most structures required for mating or reproduction are sexually dimorphic and are generated by sex-specific cell lineages. Thus to understand cell fate specification in hermaphrodites, one must consider how the body plan, which is specified during embryogenesis, influences the fates individual cells. One possible mechanism may involve the asymmetric distribution of POP-1 /Tcf, the sole C. elegans Tcf homolog, to anterior-posterior sister cells. Another mechanism that functions to specify cell fates along the anterior-posterior body axis in both hermaphrodites and males are the Hox genes. Since most of the cell fate specifications that occur in hermaphrodites also occur in males, the focus of this chapter will be on those that only occur in hermaphrodites. This will include the cell fate decisions that affect the HSN neurons, ventral hypodermal P cells, lateral hypodermal cells V5 , V6 , and T ; as well as the mesodermal M, Z1 , and Z4 cells and the intestinal cells. Both cell lineage-based and cell-signaling mechanisms of cell fate specification will be discussed. Only two direct targets of the sex determination pathway that influence cell fate specification to produce hermaphrodite-specific cell fates have been identified. Thus a major challenge will be to learn additional mechanisms by which the sex determination pathway interacts with signaling pathways and other cell fate specification genes to generate hermaphrodite-specific cell fates.
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Semin Cell Dev Biol,
2023]
The nematode Caenorhabditis elegans has been a model for studying infection since the early 2000s and many major discoveries have been made regarding its innate immune responses. C. elegans has been found to utilize some key conserved aspects of immune responses and signaling, but new interesting features of innate immunity have also been discovered in the organism that might have broader implications in higher eukaryotes such as mammals. Some of the distinctive features of C. elegans innate immunity involve the mechanisms this bacterivore uses to detect infection and mount specific immune responses to different pathogens, despite lacking putative orthologs of many important innate immune components, including cellular immunity, the inflammasome, complement, or melanization. Even when orthologs of known immune factors exist, there appears to be an absence of canonical functions, most notably the lack of pattern recognition by its sole Toll-like receptor. Instead, recent research suggests that C. elegans senses infection by specific pathogens through contextual information, including unique products produced by the pathogen or infection-induced disruption of host physiology, similar to the proposed detection of patterns of pathogenesis in mammalian systems. Interestingly, C. elegans can also transfer information of past infection to their progeny, providing robust protection for their offspring in face of persisting pathogens, in part through the RNAi pathway as well as potential new mechanisms that remain to be elucidated. Altogether, some of these strategies employed by C. elegans share key conceptual features with vertebrate adaptive immunity, as the animal can differentiate specific microbial features, as well as propagate a form of immune memory to their offspring.
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Wiley Interdiscip Rev Dev Biol,
2020]
One approach to understand the construction of complex systems is to investigate whether there are simple design principles that are commonly used in building such a system. In the context of nervous system development, one may ask whether the generation of its highly diverse sets of constituents, that is, distinct neuronal cell types, relies on genetic mechanisms that share specific common features. Specifically, are there common patterns in the function of regulatory genes across different neuron types and are those regulatory mechanisms not only used in different parts of one nervous system, but are they conserved across animal phylogeny? We address these questions here by focusing on one specific, highly conserved and well-studied regulatory factor, the POU homeodomain transcription factor UNC-86. Work over the last 30years has revealed a common and paradigmatic theme of
unc-86 function throughout most of the neuron types in which Caenorhabditis elegans
unc-86 is expressed. Apart from its role in preventing lineage reiterations during development, UNC-86 operates in combination with distinct partner proteins to initiate and maintain terminal differentiation programs, by coregulating a vast array of functionally distinct identity determinants of specific neuron types. Mouse orthologs of
unc-86, the Brn3 genes, have been shown to fulfill a similar function in initiating and maintaining neuronal identity in specific parts of the mouse brain and similar functions appear to be carried out by the sole Drosophila ortholog, Acj6. The terminal selector function of UNC-86 in many different neuron types provides a paradigm for neuronal identity regulation across phylogeny. This article is categorized under: Gene Expression and Transcriptional Hierarchies>Regulatory Mechanisms Invertebrate Organogenesis>Worms Nervous System Development>Vertebrates: Regional Development.