Kumar A et al. (2014) Nat Protoc "Dual-view plane illumination microscopy for rapid and spatially isotropic imaging."

Gandler W, Colon-Ramos DA, Christensen R, Chandris P, Bokinsky A, Rondeau G, Bao Z, McCreedy E, Kumar A, McAuliffe M, Shroff H, Wu Y

[Nat Protoc, 2014]

We describe the construction and use of a compact dual-view inverted selective plane illumination microscope (diSPIM) for time-lapse volumetric (4D) imaging of living samples at subcellular resolution. Our protocol enables a biologist with some prior microscopy experience to assemble a diSPIM from commercially available parts, to align optics and test system performance, to prepare samples, and to control hardware and data processing with our software. Unlike existing light sheet microscopy protocols, our method does not require the sample to be embedded in agarose; instead, samples are prepared conventionally on glass coverslips. Tissue culture cells and Caenorhabditis elegans embryos are used as examples in this protocol; successful implementation of the protocol results in isotropic resolution and acquisition speeds up to several volumes per s on these samples. Assembling and verifying diSPIM performance takes 6 d, sample preparation and data acquisition take up to 5 d and postprocessing takes 3-8 h, depending on the size of the data.

Christensen RP et al. (2015) Elife "Untwisting the Caenorhabditis elegans embryo."

Kovacevic I, Bokinsky A, Liu H, McCreedy E, McAuliffe M, Mohler W, Shroff H, Wu Y, Christensen RP, Marquina-Solis J, Kumar A, Winter PW, Guo M, Colon-Ramos DA, Bao Z, Tashakkori N, Santella A

[Elife, 2015]

The nematode Caenorhabditis elegans possesses a simple embryonic nervous system comprising 222 neurons, a number small enough that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open source untwisting and annotation software which allows the investigation of neurodevelopmental events in post-twitching embryos, and apply them to track the 3D positions of seam cells, neurons, and neurites in multiple elongating embryos. The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an "average" worm embryo. The untwisting and cell tracking capability we demonstrate provides a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis.

Christensen, R.P. et al. (2019) International Worm Meeting "Creating a pan-nuclear atlas in the post-twitching Caenorhabditis elegans embryo."

Levin, M., Shroff, H., Christensen, R.P., Bokinsky, A., Moyle, M., Guo, M., Mohler, W., Colon-Ramos, D., Wu, Y., McCreedy, E., Ardiel, E., Bao, Z., Karaj, N., Lauziere, A., Duncan, L., Harvey, B., Santella, A.

[International Worm Meeting, 2019]

The Caenorhabditis elegans embryo represents an excellent model system in which to study tissue formation. However, the onset of twitching and elongation makes data analysis during the second half of embryogenesis difficult. Previously, we developed software to enable computational untwisting of the C. elegans embryo, removing the effects of embryo movement and placing embryo images in a common reference frame for analysis. We have now improved our software suite to incorporate more user-friendly positional tracking and better segmentation, reducing clipping of images around the edges of the embryo. We also apply deep learning to segment nuclei in a semi-automated fashion. We apply our software to generate a map showing the position of 158 nuclei in the post-twitching worm embryo, as a partial step in the generation of a complete embryonic nuclear atlas. Tracked nuclei include 16 neurons and 81 body wall muscles. Our improved tools, combined with pre-twitching work from our collaborators on the WormGUIDES project, allow us to pursue the goal of developing a complete nuclear and neurite outgrowth atlas for the nematode embryo from the two cell stage until hatching.

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.

Christensen, R et al. (2017) International Worm Meeting "Improved untwisting software for examining development in moving C. elegans embryos."

McCreedy, E, Guo, M, Mohler, W, Colon-Ramos, D.A., Levin, M, Duncan, W, Moyle, M, Bao, Z, Shroff, H, Wu, Y, Bokinsky, A, Christensen, R, Ardiel, E, Santella, A, Harvey, B

[International Worm Meeting, 2017]

The C. elegans embryo represents an excellent system in which to examine complex, systems-level developmental events, but rapid embryo movement and elongation confound inspection of events after embryos have begun twitching. This period of time encompasses numerous developmental processes, including cell specialization, neurite outgrowth and neuronal migration, and the beginning of functional activity in the nervous system. We recently reported (Christensen et al., eLife. 2015 4:e10070) a combined imaging and data analysis pipeline to enable developmental events during this time period to be studied. We now report improvements in our untwisting strain and data analysis pipeline. We have improved our untwisting strain by incorporating a worm surface marker (lin-26p::vab-10(actin-binding domain)::GFP; Gally C, et al., Development. 2009 136(18):3109-19) to provide more accurate information about the dorsal, ventral, and lateral boundaries of the developing embryo. We have adjusted the untwisting software to segment the surface marker, leading to less dorsal-ventral clipping and better capture of embryo structure in bent regions compared to the original untwisting algorithm. We have also incorporated better segmentation of seam cell nuclei when untwisting, leading to reduced lateral clipping in untwisted images, and have added the ability to convert 3D positions between twisted and untwisted space for any volume. We apply the improved untwisting software to track the position of seam cell nuclei and E lineage intestinal nuclei. We plan to use this software to track the position of all nuclei in the embryo from the beginning of twitching until hatching, as well as the morphological development of the C. elegans nervous system during embryogenesis.

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.