Klebes A et al. (2000) European Worm Meeting "Genetic control of adherens junction assembly during embryogenesis of C. elegans"

Klebes A, Knust E, Theres C, Bossinger O, Segbert C

[European Worm Meeting, 2000]

The widespread occurrence and fundamental importance of epithelia raises the question whether the establishment and maintenance of the polarized phenotype is conserved across species. Because of its simplicity the embryonic gut epithelium of C. elegans was chosen to study these questions with a reverse genetics approach. Data shown here indicate that several aspects of the subcellular spatial organisation of epithelia are conserved, while others differ between C. elegans, Drosophilaand vertebrates. In the worm, the homolog of the Drosophila tumour-suppressor protein Discs-large, DLG-1 is restricted to the zonula adherens (ZA) of all embryonic epithelia. This deviates from the association of its homologs with the septate junction in Drosophila and the tight junction in vertebrates. RNA mediated interference (cDNA clones kindly provided by Dr. Kohara) of dlg-l, leads to fragmentation of the ZA in gut, pharynx and hypodermis and finally leads to embryonic arrest during the late morphogenesis phase. Strikingly, proteins enriched in a cortical domain, apical to the ZA, are regulated differently in dlg-1(RNAi) embryos. While expression of an atypical protein kinase C and other proteins is not altered in these embryos, the homolog of the Drosophila crumbs gene in C. elegans, crb-1 is no longer concentrated in this domain. While in Drosophila crumbs and discs-lost are essential for epithelial development, in C. elegans lack of the homologs crb-1, crumbs-like gene (crl-1) and dlt-1, singly or in combination, do not cause any obvious embryonic or adult phenotype. The future focus will be on the identification of DLG-1 binding partners in C. elegans necessary for cell adhesion in the gut epithelium.

O Bossinger et al. (1999) International C. elegans Meeting "Investigating apico-basal polarity in the embryonic gut of C. elegans"

C Segbert, C Theres, A Klebes, E Knust, O Bossinger

[International C. elegans Meeting, 1999]

The generation and maintenance of epithelial polarity relies on the correct reception of signals and cues from apical and baso-lateral sources (1). Thus, in Drosophila the Crumbs protein (2, 3) is localized apically to the zonula adherens (ZA; 4) and plays a key role in maintaining the polarized phenotype of the ectoderm and its derivatives (5). We have started to investigate epithelial polarization in the embryonic gut of C. elegans, a simple tube of 20 cells, arranged in a series of nine rings (6). Using the sequence of the Drosophila Crumbs cytoplasmic domain, we identified two C.e. homologues of CRB. We applied RNA interference technique (cDNA clones kindly provided by Dr. Kohara), in order to disturb normal development, but no visible phenotypes could be detected so far. Immuno-staining during morphogenesis of C.e. demonstrates expression of CeCRB1 in the gut and later in the pharynx, while at the same time intestinal staining is reduced. Double-labelling against phosphotyrosine reveals localization of CeCRB1 apical to the ZA in the embryonic gut of C.e. We are now concentrating on basal cues necessary for polarization of the gut epithelium and have begun to study C.e. mutants with defects in major constituents of basement membranes (e.g. let-2, emb-9, unc-52), beta-integrin (pat-3) or vinculin (deb-1). The phenotype of ZA organization in the above mutants was analyzed by confocal microscopy. It ranges from fragmentation to complete absence of the ZA. While elements of the Wnt/pop-1 signalling pathway have been postulated to act autonomously within the E-lineage for anterior-posterior patterning (7), we suggest that processing of extracellular matrix information is a prerequisite for establishing correct apico-basal polarity in the embryonic gut of C.elegans. (1) Eaton and Simons, (1995). Cell 82: 5-8; (2) Tepass et al., (1990). Cell 61: 787-799; (3) Wodarz et al., (1995). Cell: 82, 67-76; (4) Tepass, (1996). Dev. Biol. 177: 217-225; (5) Tepass and Knust, (1990). Roux´s Arch. Dev. Biol. 199: 189-206; (6) Sulston et al., (1983). Dev. Biol. 100: 64-119; (7) Schroeder and McGhee, (1998). Development 125: 4877-4887.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[Curr Biol, 2011]

Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

Schaeffer JM et al. (1990) J Antibiot (Tokyo) "Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites."

Williamson JM, Schaeffer JM, Bergstrom AR, Liesch JM, Goetz MA, Frazier EG

[J Antibiot (Tokyo), 1990]

Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.

Desta IT et al. (2016) J Lab Autom "Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing."

Giakoumidis N, Mustafa N, AlGharibeh N, Orozaliev A, Al-Sharif A, Song YA, Desta IT, Gunsalus KC

[J Lab Autom, 2016]

Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for high-throughput drug screening.