Ebbing, A.L.P. et al. (2017) International Worm Meeting "Serial-section RNA sequencing: a novel method for genome-wide gene expression pattern analysis in C. elegans."

Ebbing, A.L.P., Korswagen, H.C., van Oudenaarden, A., Betist, M.C., Vertesy, A.

[International Worm Meeting, 2017]

To advance our understanding of development and physiology, it is important to gain detailed insight into the spatial and temporal expression patterns of all genes. Such a comprehensive overview of gene expression patterns will identify cell type and organ specific genes. It will also provide a framework for studying how gene expression patterns change upon perturbation. RNA sequencing (RNA-seq) is ideally suited for genome-wide analysis of gene expression. However, RNA-seq by itself does not provide information on where genes are expressed in the organism. A solution to this problem is to include spatial information by sectioning the organism along one of the body axes and to perform RNA-seq on each of the separate sections. We have developed a serial-section RNA-seq (serial-seq) method for C. elegans. In brief, we cryo-section a young adult animal from the head to the tail into 20 micrometer thick slices, resulting in a total of 40 to 50 slices. Each slice is then sequenced using the sensitive CEL-seq method and the sequencing data is aligned to create an anteroposterior gene expression map. Using this approach, an average of 8794 genes (43% of coding genes) (n=8) can be detected along the length of the animal. These include genes that are expressed in major tissues such as the germline, but also genes that are known to be expressed in only single neuron pairs in the head, demonstrating the high sensitivity of our approach. Furthermore, we found that these expression patterns are highly reproducible among independently sectioned animals. What makes serial-seq particularly powerful in C. elegans is its relatively simple and invariant anatomy. Because each slice contains only a limited number of cells, we can predict which cells are in the different slices and use this information to identify cell type specific genes. Furthermore, we have developed an algorithm that enables us to search for genes with specific expression patterns. Using known marker genes as a starting point, we have identified genes that are specifically expressed in the germline and sperm, in organ structures such as the pharynx, the intestine, the vulva, the spermatheca and the male reproductive tract, and in neurons of the nerve ring and tail ganglia. The ability to identify cell type specific genes is an important advantage over RNA-seq of isolated cells, which does not distinguish between specific and more generally expressed genes. In summary, we have generated high-resolution anteroposterior gene expression maps of C. elegans, including maps of hermaphrodites, males and germline deficient mutants. In addition to providing an expression pattern resource, serial-seq is a powerful method for studying gene expression pattern changes at the whole-genome level.

Ebbing, A.L.P. et al. (2017) International Worm Meeting "Serial-section RNA sequencing: genome-wide gene expression pattern analysis in C. elegans males and hermaphrodites."

Vertesy, A., Betist, M.C., Korswagen, H.C., van Oudenaarden, A., Ebbing, A.L.P.

[International Worm Meeting, 2017]

RNA sequencing (RNA-seq) is ideally suited for genome-wide analysis of gene expression. However, when a whole organism is used for RNA isolation and sequencing, the data will show the overall level of gene expression, but not where such genes are expressed in the organism. A solution to this problem is to provide spatial information by sectioning the organism along one (or more) of the body axes and to perform RNA-seq on each of the separate sections. We have developed a serial-section RNA-seq (serial-seq) method for C. elegans (see also the other abstract of Ebbing, Korswagen and co-workers). In brief, we cryo-section a young adult animal from the head to the tail into 20 micrometer thick slices, resulting in a total of 40 to 50 slices. Each slice is then sequenced using the sensitive CEL-Seq method and the sequencing data is aligned to create a high-resolution anteroposterior gene expression map. We have generated expression maps for 4 young adult hermaphrodites, 4 young adult males and 2 germline deficient glp-1 mutants. In these datasets, an average of 8794 genes (43% of coding genes) can be detected along the length of the animal. These include genes that are expressed in major tissues such as the germline, but also genes that are known to be expressed in only single neuron pairs in the head, demonstrating the high sensitivity of our approach. Furthermore, we found that these expression patterns are highly reproducible among independently sectioned animals. To explore these gene expression maps, we have developed an algorithm that enables us to search for genes with specific expression patterns. Using the expression patterns of known marker genes as a starting point, we have identified genes that are specifically expressed in the germline and sperm, in organ structures such as the pharynx, the intestine, the vulva, the spermatheca and the male reproductive tract, and in neurons of the nerve ring and tail ganglia. Furthermore, we have found extensive sex-specific differences in gene expression in the germline and sperm, in the male reproductive tract and in the male specific CEM neurons. We will present an overview of the method and discuss our findings on cell, organ and sex-specific gene expression patterns.

Ebbing A et al. (2018) Dev Cell "Spatial Transcriptomics of C.elegans Males and Hermaphrodites Identifies Sex-Specific Differences in Gene Expression Patterns."

Junker JP, Ebbing A, Korswagen HC, Spanjaard B, Berezikov E, Betist MC, van Oudenaarden A, Vertesy A

[Dev Cell, 2018]

To advance our understanding of the genetic programs that drive cell and tissue specialization, it is necessary to obtain a comprehensive overview of gene expression patterns. Here, we have used spatial transcriptomics to generate high-resolution, anteroposterior gene expression maps of C.elegans males and hermaphrodites. To explore these maps, we have developed computational methods for discovering region- and tissue-specific genes. We have found extensive sex-specific gene expression differences in the germline and sperm and discovered genes that are specifically expressed in the male reproductive tract. These include a group of uncharacterized genes that encode small secreted proteins that are required for male fertility. We conclude that spatial gene expression maps provide a powerful resource for identifying tissue-specific gene functions in C.elegans. Importantly, we found that expression maps from different animals can be precisely aligned, enabling transcriptome-wide comparisons of gene expression patterns.

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.