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The specification of a germ cell as sperm or oocyte and determination of cell number remain unsolved questions in developmental biology. This paper examines Caenorhabditis elegans FOG-1, a CPEB-related RNA-binding protein that controls the sperm fate. We find that abundant FOG-1 protein is observed transiently in germ cells just prior to their expression of an early sperm-differentiation marker. As the germline tissue elongates, abundant FOG-1 appears more and more distally as sperm become specified, but disappears when the germ line switches to oogenesis. This dynamic pattern is controlled by both globally acting and germline-specific sex-determining regulators. Importantly, the extent of FOG-1 expression corresponds roughly to sperm number in wild-type and mutants, altering sperm number. By contrast, three other key regulators of the sperm/oocyte decision do not similarly correspond to sperm number. We suggest that FOG-1 is precisely modulated in both time and space to specify sperm fate and control sperm number. 相似文献
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E proteins are conserved regulators of growth and development. We show that the Caenorhabditis elegans E-protein helix–loop–helix-2 (HLH-2) functions as a homodimer in directing development and function of the anchor cell (AC) of the gonad, the critical organizer of uterine and vulval development. Our structure–function analysis of HLH-2 indicates that dimerization drives its degradation in other uterine cells (ventral uterine precursor cells [VUs]) that initially have potential to be the AC. We also provide evidence that this mode of dimerization-driven down-regulation can target other basic HLH (bHLH) dimers as well. Remarkably, human E proteins can functionally substitute for C. elegans HLH-2 in regulating AC development and also display dimerization-dependent degradation in VUs. Our results suggest that dimerization-driven regulation of bHLH protein stability may be a conserved mechanism for differential regulation in specific cell contexts. 相似文献
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Sasagawa Y Yamanaka K Saito-Sasagawa Y Ogura T 《Genes to cells : devoted to molecular & cellular mechanisms》2010,15(12):1201-1215
UBX (ubiquitin regulatory X) domain-containing proteins act as cofactors for CDC-48/p97. CDC-48/p97 is essential for various cellular processes including retro-translocation in endoplasmic reticulum-associated degradation, homotypic membrane fusion, nuclear envelope assembly, degradation of ubiquitylated proteins, and cell cycle progression. CDC-48/p97-dependent processes are determined by differential binding of cofactors including UBX proteins, but the cellular functions of UBX proteins have not yet been elucidated, especially in multicellular organisms. Therefore, we investigated the functions of UBX family members using Caenorhabditis elegans, which expresses six UBX proteins, UBXN-1 to UBXN-6. All six UBXN proteins directly interacted with CDC-48.1 and CDC-48.2, and simultaneous knockdown of the expression of three genes, ubxn-1, ubxn-2 and ubxn-3, induced embryonic lethal and sterile phenotypes, but knockdown of either one or two did not. The sterile worms had a feminized germ-line phenotype, producing oocytes but no sperm. UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm. TRA-1A, which is a key factor in the sex determination pathway and inhibits spermatogenesis, accumulated in worms in which UBXN-1, UBXN-2 and UBXN-3 had been simultaneously knocked down. Taken together, these results suggest that UBXN-1, UBXN-2 and UBXN-3 are redundant cofactors for CDC-48/p97 and control spermatogenesis via the degradation of TRA-1A. 相似文献
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Watanabe N Ishihara T Ohshima Y 《Genes to cells : devoted to molecular & cellular mechanisms》2007,12(5):603-609
Body size determination is critical for multicellular organisms; however, the mechanisms remain largely unknown. Mutations that alter body size were studied to solve the mechanisms, for example, in mouse, fruit fly and the nematode Caenorhabditis elegans. In C. elegans, a large mutant and several small body size (sma) mutants are known. Of the latter, sma-2, sma-3, sma-4, sma-6, dbl-1 and daf-4 have a mutation in the components of the DBL-1/TGFbeta signal pathway, and sma-5 in a MAP kinase homologue. We have constructed double mutants carrying two of such small body size mutations, sma-5 and sma-4 or sma-2. They are much smaller than either of the parental single mutants, indicating that the sma-5 gene functions independently of the DBL-1/TGFbeta pathway. We show that their body volumes are as small as 1/10 of that of the wild-type, and that the sizes of major organs are much reduced, by the methods previously developed by us. But the numbers of cells are not changed, suggesting that the cells are very small. These results highlight surprising flexibility of body size and cell size in a multicellular organism, which will give a novel insight into the mechanisms of body size control. 相似文献
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Spermatogenesis is a highly complex, hormonally regulated cytodifferentiation process finally leading to the production of spermatozoa. In addition to other events germ cell differentiation is characterized by a gradual structural modification of many organelles including mitochondria which play a unique role. The morphological and functional development of germ cell mitochondria is a reflection of the permanent change in the testicular microenvironment which occurs when the germ cells are slowly moving from the base of the seminiferous epithelium to the lumen. Concomitant with the structural changes, several mitochondrial proteins are known to be expressed and synthesized during distinct phases of the organelle's development. This review pays particular attention to these transiently expressed mitochondrial proteins such as hsp60, Lon protease, sulphydryl oxidase and cytochrome ct. Furthermore, the biological function of this stepwise gene activation during mitochondrial and germ cell development is discussed. 相似文献
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One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction. 总被引:2,自引:0,他引:2
We describe an electrophysiological preparation of the neuromuscular junction of the nematode C. elegans, which adds to its considerable genetic and genomic resources. Mutant analysis, pharmacology and patch-clamp recording showed that the body wall muscles of wild-type animals expressed a GABA receptor and two acetylcholine receptors. The muscle GABA response was abolished in animals lacking the GABA receptor gene unc-49. One acetylcholine receptor was activated by the nematocide levamisole. This response was eliminated in mutants lacking either the unc-38 or unc-29 genes, which encode alpha and non-alpha acetylcholine receptor subunits, respectively. The second, previously undescribed, acetylcholine receptor was activated by nicotine, desensitized rapidly and was selectively blocked by dihydro-beta-erythroidine, thus explaining the residual motility of unc-38 and unc-29 mutants. By recording spontaneous endogenous currents and selectively eliminating each of these receptors, we demonstrated that all three receptor types function at neuromuscular synapses. 相似文献
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The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these genes have been found in several species. Whereas in humans NMD is linked to splicing, PTC definition occurs independently of exon boundaries in Drosophila. Here, we have conducted an analysis of the cis-acting sequences and trans-acting factors that are required for NMD in C. elegans. We show that a PTC codon is defined independently of introns in C. elegans and, consequently, components of the exon junction complex (EJC) are dispensable for NMD. We also show a distance-dependent effect, whereby PTCs that are closer to the 3' end of the mRNA are less sensitive to NMD. We also provide evidence for the existence of previously unidentified components of the NMD pathway that, unlike known smg genes, are essential for viability in C. elegans. A genome-wide RNA interference (RNAi) screen resulted in the identification of two such novel NMD genes, which are essential for proper embryonic development, and as such represent a new class of essential NMD genes in C. elegans that we have termed smgl (for smg lethal). We show that the encoded proteins are conserved throughout evolution and are required for NMD in C. elegans and also in human cells. 相似文献
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OBJECTIVE: Living organisms have mechanisms to adapt to various conditions of external environments. If we can realize these mechanisms on the computer, it may be possible to apply methods of biological and biomimetic adaptation to the engineering of artificial machines. This paper focuses on the nematode Caenorhabditis elegans (C. elegans), which has a relatively simple structure and is one of the most studied multicellular organisms. We aim to develop its computer model, artificial C. elegans, to analyze control mechanisms with respect to motion. Although C. elegans processes many kinds of external stimuli, we focused on gentle touch stimulation. METHODS: The proposed model consists of a neuronal circuit model for motor control that responds to gentle touch stimuli and a kinematic model of the body for movement. All parameters included in the neuronal circuit model are adjusted by using the real-coded genetic algorithm. Also, the neuronal oscillator model is employed in the body model to generate the sinusoidal movement. The motion velocity of the body model is controlled by the neuronal circuit model so as to correspond to the touch stimuli that are received in sensory neurons. CONCLUSION: The computer simulations confirmed that the proposed model is capable of realizing motor control similar to that of the actual organism qualitatively. By using the artificial organism it may be possible to clarify or predict some characteristics that cannot be measured in actual experiments. With the recent development of computer technology, such a computational analysis becomes a real possibility. The artificial C. elegans will contribute for studies in experimental biology in future, although it is still developing at present. 相似文献
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Chi-Hao Luan Shihong Qiu James B. Finley Mike Carson Rita J. Gray Wenying Huang David Johnson Jun Tsao Jrme Reboul Philippe Vaglio David E. Hill Marc Vidal Lawrence J. DeLucas Ming Luo 《Genome research》2004,14(10B):2102-2110
Proteome-scale studies of protein three-dimensional structures should provide valuable information for both investigating basic biology and developing therapeutics. Critical for these endeavors is the expression of recombinant proteins. We selected Caenorhabditis elegans as our model organism in a structural proteomics initiative because of the high quality of its genome sequence and the availability of its ORFeome, protein-encoding open reading frames (ORFs), in a flexible recombinational cloning format. We developed a robotic pipeline for recombinant protein expression, applying the Gateway cloning/expression technology and utilizing a stepwise automation strategy on an integrated robotic platform. Using the pipeline, we have carried out heterologous protein expression experiments on 10,167 ORFs of C. elegans. With one expression vector and one Escherichia coli strain, protein expression was observed for 4854 ORFs, and 1536 were soluble. Bioinformatics analysis of the data indicates that protein hydrophobicity is a key determining factor for an ORF to yield a soluble expression product. This protein expression effort has investigated the largest number of genes in any organism to date. The pipeline described here is applicable to high-throughput expression of recombinant proteins for other species, both prokaryotic and eukaryotic, provided that ORFeome resources become available. 相似文献
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The nematode Caenorhabditis elegans is excellently suited as a model for studying the genetic and molecular genetic basis of aging, and to test chemical compounds that interfere with the aging process. Mutants of factors in both the insulin and target of rapamycin (TOR) signalling pathways have been shown to extend life span of the worm. Phenotypic similarities among those mutants suggested that, exploiting the corresponding phenotypes in a semiautomated way, may increase the speed of investigating life span and aging in C. elegans. Here, we discuss several methodological approaches to automate longevity assays in the nematode. 相似文献
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Evan L. Ardiel 《Journal of neurogenetics》2013,27(3):239-255
This review outlines research into the cellular and molecular mechanisms underlying a simple behavior in the soil-dwelling nematode, C. elegans. A tap administered to the side of a petri plate acts as a nonlocalized mechanical stimulus to the worms within. Most adult worms respond to this tap stimulus with backward locomotion, an action known as the tap-withdrawal response. This behavior has been thoroughly characterized and the neural circuit mediating it has been determined. The response habituates following repeated stimulation, and current work is aimed at elucidating the mechanism behind this simple form of nonassociative learning. Changes in cell excitability and the strength of glutamatergic synapses play key roles in mediating this plasticity. 相似文献
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Functional silencing of chromosomal loci can be induced by transgenes (cosuppression) or by introduction of double-stranded RNA (RNAi). Here, we demonstrate the generality of and define rules for a transgene-mediated cosuppression phenomenon in the Caenorhabditis elegans germ line. Functional repression is not a consequence of persistent physical association between transgenes and endogenous genes or of mutations in affected genes. The cosuppression mechanism likely involves an RNA mediator that defines its target specificity, reminiscent of RNAi. Cosuppression is strongly abrogated in rde-2 and mut-7 mutants, but is not blocked in an rde-1 mutant, indicating that cosuppression and RNAi have overlapping but distinct genetic requirements. 相似文献
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Short tandem repeats (STRs) represent an important class of genetic variation that can contribute to phenotypic differences. Although millions of single nucleotide variants (SNVs) and short indels have been identified among wild Caenorhabditis elegans strains, the natural diversity in STRs remains unknown. Here, we characterized the distribution of 31,991 STRs with motif lengths of 1–6 bp in the reference genome of C. elegans. Of these STRs, 27,667 harbored polymorphisms across 540 wild strains and only 9691 polymorphic STRs (pSTRs) had complete genotype data for more than 90% of the strains. Compared with the reference genome, the pSTRs showed more contraction than expansion. We found that STRs with different motif lengths were enriched in different genomic features, among which coding regions showed the lowest STR diversity and constrained STR mutations. STR diversity also showed similar genetic divergence and selection signatures among wild strains as in previous studies using SNVs. We further identified STR variation in two mutation accumulation line panels that were derived from two wild strains and found background-dependent and fitness-dependent STR mutations. We also performed the first genome-wide association analyses between natural variation in STRs and organismal phenotypic variation among wild C. elegans strains. Overall, our results delineate the first large-scale characterization of STR variation in wild C. elegans strains and highlight the effects of selection on STR mutations.Short tandem repeats (STRs) are repetitive elements consisting of 1–6 bp DNA sequence motifs that provide a large source for genetic variation in both inherited and de novo mutations (Willems et al. 2016; Fotsing et al. 2019). The predominant mechanism of STR mutations is DNA replication slippage, which often causes expansion or contraction in the number of repeats (Mirkin 2007; Gemayel et al. 2010). Because of their intrinsically unstable nature, STRs have orders of magnitude higher mutation rates than other types of mutations, such as single nucleotide variants (SNVs) and short insertions or deletions (indels) (Lynch 2010; Sun et al. 2012; Willems et al. 2016; Gymrek et al. 2017). The precise mutation rates of STRs are highly variable across different loci and are affected by motif sequences and repeat lengths (Legendre et al. 2007). In humans, STRs are estimated to constitute about 3% of the genome and are associated with dozens of diseases (Mirkin 2007; Hannan 2018; Malik et al. 2021). Emerging studies have also revealed the role of STRs in regulation of gene expression and complex traits in humans and other organisms, which were suggested to facilitate adaptation and accelerate evolution (Fotsing et al. 2019; Jakubosky et al. 2020; Reinar et al. 2021).The free-living nematode Caenorhabditis elegans is a keystone model organism that has been found across the world (Brenner 1974; Kiontke et al. 2011; Andersen et al. 2012; Félix and Duveau 2012; Cook et al. 2017; Crombie et al. 2019, 2022; Lee et al. 2021). The C. elegans Natural Diversity Resource (CeNDR) catalogs and distributes thousands of wild strains, genome sequence data, and genome-wide variation data, including SNVs and short indels (Andersen et al. 2012; Cook et al. 2017; Evans et al. 2021a). Numerous C. elegans population genomics studies and genome-wide association (GWA) studies have leveraged CeNDR resources, such as the genetic variant data across wild strains and the GWA mapping pipeline (Snoek et al. 2020; Lee et al. 2021; Evans et al. 2021a; Gilbert et al. 2022; Widmayer et al. 2022; Zhang et al. 2022). However, the natural diversity in C. elegans STRs and their impacts on organism-level and molecular traits among wild strains remain unknown because of the lack of STR variation characterization. STRs are challenging to genotype because of their repetitive nature causing errors such as “PCR stutters” (Gymrek 2017). Recent advances provided opportunities to identify genome-wide STR variation accurately in large scales using high-throughput sequencing data (Willems et al. 2017).In this work, we focused on characterization of STRs with motif lengths of 1–6 bp in the reference genome of C. elegans and identified their natural variation across 540 genetically distinct wild strains. Using these data, we analyzed mutations, diversity, and how selection occurred in the STR loci. We also investigated the possible impacts of STR variation on phenotypic variation across wild C. elegans strains. 相似文献
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在后生动物的发育中 ,程序性细胞死亡 (PCD)在组织的塑型、神经元间的精细连接、多余细胞或损伤细胞的消除等诸多方面扮演重要角色。通过PCD方式 ,正在死亡的细胞迅速被吞噬细胞包裹清除。在线虫体内 ,PCD需要杀手基因 (killergenes)egl- 1、ced - 4和ced - 3等的协同作用 ,而正在死亡细胞的吞噬过程 (engulfment)则由ced - 1、ced -2、ced - 5、ced - 6、ced - 7、ced - 10、ced - 12等吞噬基因 (engulfmentgenes)协同完成。根据基因相互作用的基础 ,将线虫的… 相似文献
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SUT-1 enables tau-induced neurotoxicity in C. elegans 总被引:1,自引:0,他引:1
We previously reported a transgenic Caenorhabditis elegans model for tauopathies in which expression of human tau in neurons caused insoluble phosphorylated tau accumulation, neurodegeneration and uncoordinated movement (Unc). To identify genes participating in tau neurotoxicity, we conducted a forward genetic screen for mutations that ameliorate tau-induced uncoordination. The recessive mutation sut-1(bk79) partially suppresses the Unc phenotype, tau aggregation and neurodegenerative changes caused by tau. We identified the sut-1 gene and found it encodes a novel protein. We conducted a yeast two hybrid screen to identify SUT-1 binding partners and found UNC-34, the C. elegans homolog of the cytoskeletal regulatory protein Enabled (ENA). In vitro protein binding assays and genetic studies validated the interaction between SUT-1 and UNC-34. The SUT-1/UNC-34 protein-protein interaction plays a role in both the normal function of UNC-34 and in the tau-induced phenotype. Thus, we have found a conserved molecular pathway participating in tau neurotoxicity in C. elegans. 相似文献