Monica C. Vella et al. (2005) WormBook "C. elegans microRNAs."

Monica C. Vella, Frank J. Slack

[WormBook, 2005]

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7 . Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3'' untranslated region (UTR) to repress LIN-14 , while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3'' UTR to down-regulate LIN-41 . Two other miRNAs, lsy-6 and mir-273 , control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

Freeman MN et al. (1999) "Standardization of a soil bioassay using the nematode Caenorhabditis elegans"

Williams PL, Peredney CL, Freeman MN

[1999]

Caenorhabditis elegans is a free-living soil nematode that is commonly used as a biological model. Recently, much work has been done using the nematode as a toxicological model as well. Much of the work involving C. elegans has been performed in aquatic media, since it lives in the interstitial water of soil. However, testing in soil would be expected to more accurately reproduce the organism's normal environment and may take into consideration other factors not available in an aquatic test, i.e., toxicant availability effects due to sorption, various chemical interactions, etc. This study used a modification of a previous experimental protocol to determine 24h LC50 values for Cu in a Cecil series soil mixture, and examined the use of CuCl2 as a reference toxicant for soil toxicity testing with C. elegans. Three different methods of determining percent lethality were used, each dependent on how the number of worms missing after the recovery process was used in the lethality calculations. Only tests having >/= 80% worm recovery and >/= 90% control survival were used in determining the LC50S, by Probit analysis. The replicate LC50 values generated a control chart for each method of calculating percent lethality. The coefficient of variation (CV) for each of the three methods was </= 14%. The control charts and the protocol outlined in this study are intended to be used to assess test organism health and to monitor precision of future soil toxicity tests with C.

Zuckerman BM (1983) "The free-living nematode C. elegans as a rapid screen for compounds to retard aging."

Zuckerman BM

[1983]

The advantages of the free-living nematode Caenrohabditis elegans as a model for pharmacologic, toxicant and anthelmintic testing have become apparent to many companies, and the application of this organism as a primary screen for test compounds or toxic agents has expanded rapidly. It is appropriate to briefly summarize some of this nematode's qualities, to invoke an appreciation of this elegant system. As true of many invertebrate test organisms, C. elegans is small (about 1 mm X 40 u at maturity) and has a short life cycle: reproduction starts on day 3-4, ceases by day 14 and by day 25 it dies. Thus, for aging studies, all the symptoms of senescence are compressed into a short time period. In addition, this nematode has a small, fixed number of cells (about 830 at maturity) and differentiated organ systems: nervous, excretory, muscular, digestive and reproductive. The preceding characteristics are not unique in invertebrate model systems and their enumeration fails to explain the increasing popularity of C. elegans as a test organism. To understand this phenomenon several additional facts must be emphasized. First, the selection of C. elegans for detailed studies on the genetic control and regulation of behavior and developmental processes has fostered a wealth of knowledge on its neuroanatomy, cell lineages, biochemistry and behavior. There is now undoubtedly more accumulated knowledge on C. elegans than on any other multicellular creature. It is also the largest metazoan which can be continuously cultured on a chemically defined medium, and though most studies have proceeded on undefined media or in monoxenic culture (utilizing a bacterium as a food source), this property can be exploited for precise nutritional studies. In regard to aging studies, the question of relevance of aging in the nematode to that in mammals has been answered in respect to some parameters which characterize senescence in humans, and further study will define other features of aging which are common to all metazoa. In practical terms, this means that test which require 24-36 months to rear an aged rat for evaluation of a pharmaceutical, can potentially be accomplished in 21 days using the nematode. The paper emphasizes that the use of the C. elegans system as a primary screen for candidate compounds to intervene in the aging process can save time, effort and money, while