tharris's Li:Y [26 articles]

Abstract

"Acetyl-CoA carboxylase (ACC) is a key enzyme in biosynthesis of fatty acids, which serve essential cellular functions in energy storage, membrane structure, and signaling. In Caenorhabditis elegans, W09B6.1 is known ACC homologous gene whereas its point mutant pod-2 is known to produce a embryonic lethal phenotype, polarity defects, and an osmotic-sensitive phenotype. Here, we further characterized the role of ACC in C. elegans through expression of transgenic ACC (WO9B6.1::GFP) and WO9B6.1 RNAi feeding. Transgenic ACC was primarily localized to the hypodermis ...

Abstract

Background: We investigated the effects of chronic ethanol exposure on physical development, reproduction, and life expectancy of Caenorhabditis elegans, a microscopic nematode worm. It has a small nervous system of 302 neurons and a short lifespan of 2 to 3 weeks. Methods: In this study, the worms were chronically exposed to varying concentrations of ethanol for different periods of their life: for their entire lifespan, during larval development only, and during adulthood only. In addition, the worms were exposed to ethanol ...

Abstract

Human movement disorders represent a significant societal burden. Early onset torsion dystonia (EOTD) is one such disorder characterized by sustained muscle contractions that frequently cause repetitive movements or abnormal postures. EOTD is caused by a dominant mutation in the DYT1 gene where a single glutamic acid residue of the affected protein, torsinA, is deleted in frame (<font face=symbol>D</font>E). Therapeutic options for EOTD are currently limited and involve either surgery or chemodenervation via injection of botulinum toxin. TorsinA is a member ...

Abstract

Nervous system deficits in fetal alcohol spectrum disorder had been investigated extensively in multiple animal models such as rodents, pig, sheep, fish, and insects (Cudd, 2005). However, fundamental molecular and genetic alteration and interaction with alcohol that result in cognitive and behavioral abnormalities are difficult to dissect in higher order animals due to the complexity of their nervous systems and behavior. Here we attempt to develop a model in which both chronic and acute embryonic exposure of ethanol can be ...

Abstract

Neuropeptides are an important class of signaling molecules involved in nervous system function. The C. elegans gene flp-18 is predicted to encode six distinct neuropeptides of the FMRFamide family. We found that a transgene carrying extra copies of flp-18 causes multiple behavioral abnormalities, including a characteristically coiled posture, uncoordinated reverse locomotion, increased spontaneous reversal frequency, and a Sho (suppression-of-head oscillation) phenotype. We have isolated a flp-18 deletion allele, n4766, in which all the neuropeptide-encoding sequences are absent. In contrast to ...

Abstract

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 °C and 24 °C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains ...

Abstract

Expansion of CTG repeat within the 3”-untranslated region of the DMPK gene causes the most common neuromuscular disorder, myotonic dystrophy type 1 (DM1), through a RNA trans-dominant mechanism. Here, we explore Caenorhabditis elegans as a model system to investigate the repeat size-dependent toxic effect by expression of green fluorescent protein (GFP) transcripts with various lengths of untranslatable CUG repeats (CUG5, CUG30, CUG83, CUG125, and CUG213) in body wall muscles. CUG213 animals died during embryogenesis or showed retarded growth at larval stages ...

Abstract

Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. elegans and apply this technique to investigate the ways in which naphthalene and PDCB may promote tumorigenesis in mammals. We show that naphthalene and PDCB inhibit apoptosis in C. elegans, a result that suggests a ...

Abstract

Daniel L. Motola1, Carolyn L. Cummins1, Veerle Rottiers3, Kamalesh K.Sharma2, Tingting Li1, Yong Li4, Kelly Suino-Powell4, H. Eric Xu4, Richard J. Auchus2, Adam Antebi3, and David J. Mangelsdorf1. The C. elegans orphan nuclear receptor, DAF-12, lies at the convergence of signaling pathways that couple environmental cues such as food availability, temperature, and population density to the choice between reproductive development or the formation of the long-lived, stress-resistant dauer larva [1]. Genetic dissection of these signaling pathways suggests that in favorable environments ...

Abstract

In response to environmental and dietary cues, the C. elegans orphan nuclear receptor, DAF-12, regulates dauer diapause, reproductive development, fat metabolism, and life span. Despite strong evidence for hormonal control, the identification of the DAF-12 ligand has remained elusive. In this work, we identified two distinct 3-keto-cholestenoic acid metabolites of DAF-9, a cytochrome P450 involved in hormone production, that function as ligands for DAF-12. At nanomolar concentrations, these steroidal ligands (called dafachronic acids) bind and transactivate DAF-12 and rescue the hormone ...

Abstract

MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that constitute up to an estimated 1% of the total number of genes in animal genomes, including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana, M., Rauhut, R., Lendeckel, W. M Tuschl, T. (2001) Science 294, 853-858; Lai, E. C., Tomancak, P., Williams, R. W. M Rubin, G.M. (2003) Genome Biol. 4, R42; Lau, N. C., Lim, L. P., Weinstein, E. G. M Bartel, D. P. (2001) Science 294, 858-862; Lee, R. ...

Abstract

ADP-ribosylation factor (Arf) and Arf-like (Arl) proteins are a family of highly conserved 21 kDa GTPases that emerged early in the evolution of eukaryotes. These proteins serve regulatory roles in vesicular traffic, lipid metabolism, microtubule dynamics, development, and likely other cellular processes. We found evidence for the presence of 6 Arf family members in the protist Giardia lamblia and 22 members in mammals. A phylogenetic analysis was performed to delineate the evolutionary relationships among Arf family members and to attempt to ...

Abstract

To address how cell proliferation, differentiation, and morphogenesis are coordinated during organogenesis, we are studying gonadogenesis in C. elegans . In wild-type hermaphrodites, 12 somatic gonadal cells are generated by early L2. By L3, ten of these cells coalesce into the gonad center to form the somatic gonadal primordium (SGP), while the two distal tip cells (DTC) remain at the gonad ends. The DTCs and anchor cell (AC) differentiate at this stage, while the remaining cells divide further during L3 and ...

Abstract

We have been continuing to work on protocols for fixation, staining and embedding and want to share our results with the nematode community. Representative micrographs will be shown and protocols will be available for anyone interested. ...

Abstract

During organogenesis, cells acquire distinct fates and collaborate to form a complex structure. To understand this process, we are studying genes that control development of the somatic gonad in C. elegans. The gonad is founded by two progenitor cells (Z1, Z4). In hermaphrodites, Z1 and Z4 generate 12 cells in L1-L2. Ten cells then come together to form the somatic gonadal primordium (SGP). Fates of some gonadal cells are determined by this stage, some by cell-cell communication, some by lineage. Later, ...

Abstract

Transmission electron microscopy provides a precise and direct method for observing the ultrastructure of C. elegans. We have been modifying and streamlining protocols for chemical fixation, staining and embedding. Our current procedures are derived from protocols kindly provided by the Horvitz and Priess labs. We have been pleased with our results and want to share our procedures with the general nematode community. Representative micrographs will be shown and protocols will be available for anyone interested. ...

Abstract

In the wild-type C. elegans germ line, the partially cellularized nuclei ("cells") near the distal tip are a mitotic stem population. These cells exit mitosis at about 20 cell diameters from the distal tip, transit into meiotic pachytene in the remainder of the distal arm and around the bend, and undergo gametogenesis in the proximal arm. How are these different cell fates specified within the germ line? A gene on chromosome I, gld-2, is involved in a cell fate decision between ...

Abstract

ADP-ribosylation factors (ARFs) are highly conserved, 21 kDa GTPases with regulatory roles in vesicular traffic, lipid metabolism, and likely other essential cellular processes. The functions of ARFs, and the structurally related ARF-like (ARL) proteins, have been extensively explored biochemically in mammalian and yeast cells but no evidence has emerged to explain the redundancy (6 mammalian ARFs plus more than 8 ARLs) in this family. Mammalian cells express all ARF isoforms in all tissues examined. Homology searches of the worm genome have ...

Abstract

In fission yeast, Scd1/Ral1 is a putative guanine nucleotide exchange factor for Cdc42sp and also acts as a Ras1 effector necessary for the regulation of cytoskeleton organization. In this study, we have characterized a protein, Moe1, that binds directly to Scd1. A moe1 null (Delta) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Delta mutants are resistant to microtubule destabilizing agents; moreover, moe1Delta rescued the growth defects of tubulin mutants containing unstable microtubules. These ...

Abstract

Mutations in the Drosophila rdgB gene, which encodes a transmembrane phosphatidylinositol transfer protein (PITP), cause a light-enhanced retinal degeneration. Cloning of mammalian rdgB orthologs (mrdgB) reveal predicted proteins that are 39% identical to rdgB, with highest homology in the N-terminal PITP domain (62%) and in a region near the C terminus (65%). The human mrdgB gene spans approximately 12 kb and maps to 11q13.1, a locus where several retinal diseases have also been mapped. Murine mrdgB maps to a syntenic region ...

Abstract

The related dense body and M-line structures that are found in C. elegans body wall muscle cells are integrin-based transmembrane attachments that couple the basal lamina to the muscle cell cytoskeleton. In an effort to genetically dissect the assembly of dense body and M-lines, we have been studying mutants with the Pat (Paralyzed, Arrested elongation at Two-fold) phenotype. To date all of the molecularly isolated genes associated with the Pat phenotype are known to encode dense body components, includingunc-52 (UNC-52/perlecan) (1), ...

Abstract

The prompt clearance of cells undergoing apoptosis is critical during embryonic development, normal tissue turnover, as well as inflammation and autoimmunity. The molecular details of the engulfment of apoptotic cells are not fully understood. ced-6 and its human homologue gulp, encode an adapter protein, whose function in engulfment is highly evolutionarily conserved; however, the upstream and downstream components of CED-6 mediated signaling are not known. Recently, ced-1 has been shown to encode a transmembrane protein on phagocytic cells, with two functional ...

Abstract

Phospholipid-dependent kinase 1 (PDK 1) is a 3'-phospholipid-responsive serine/threonine kinase that plays a critical role in cell survival by phosphorylating and activating the anti-apoptotic AKT/PKB kinase, While PDK 1 is clearly an important component of the cell survival machinery, the potential for phospholipid-independent activation of the AKT/PKB survival pathway has not been extensively examined at the molecular level. We have identified a second form of PDK 1 in the nematode Caenorhabditis elegans that we have termed PIAK. (phospholipid-independent AKT/PKB kinase). PIAK ...

Abstract

Centrosome duplication is a critical step in assembly of the bipolar mitotic spindle, but the molecular mechanisms regulating this process during the cell cycle and during animal development are poorly understood. Here, we report that the zyg-1 gene of Caenorhabditis elegans is an essential regulator of centrosome duplication. ZYG-1 is a protein kinase specifically required for daughter centriole formation that localizes transiently to centrosomes and acts at least one cell cycle prior to each spindle assembly event. In the embryo, ZYG-1 ...

Abstract

In wild-type Caenorhabditis elegans, the hermaphrodite gonad is a symmetrical structure, whereas the male gonad is asymmetric. Two cellular processes are critical for the generation of these sexually dimorphic gonadal shapes during early larval development. First, regulatory "leader" cells that control tube extension and gonadal shape are generated. Second, the somatic gonadal precursor cells migrate and become rearranged to establish the adult pattern. In this paper, we introduce sys-1, a gene required for early organization of the hermaphrodite, but not the ...

Abstract

In wild-type Caenorhabditis elegans, the gonad is a complex epithelial tube that consists of long arms composed predominantly of germline tissue as well as somatic structures specialized for particular reproductive functions. In gon-1 mutants, the adult gonad is severely disorganized with essentially no arm extension and no recognizable somatic structure. The developmental defects in gon-1 mutants are limited to the gonad; other cells, tissues, and organs appear to develop normally. Previous work defined the regulatory "leader" cells as crucial for extension ...