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[
1992]
Caenorhabditis elegans is a small soil nematode which is currently being extensively studied to discern general principles of how genes control development. The short life cycle, ability to culture in quantities sufficient for biochemical work, well-developed genetics, small cell number for a rather sophisticated animal, and rapidly increasing possibilities for molecular genetics are features that make this species a very productive system
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[
1990]
Induction of the C. elegans vulva is a simple example of pattern formation in which the combined action of two intercellular signals specifies three cell types in a precise spatial pattern. These two signals, a graded inductive signal and a short-range lateral signal, are each mediated by a distinct genetic pathway. To understand how these intercellular signals specify cell type, we are studying, by genetic analysis and molecular cloning, genes whose products are involved in the induction pathway.
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[
1996]
Species with short life spans have been the primary targets for studies into the genetic basis of the aging process(es). Almost all genetic studies of aging and longevity have been performed on invertebrates. Invertebrates often have very short life spans, and this fact, together with the excellent genetic systems available for some yeasts, Drosophila melanogaster, and the nematode Caenorhabditis elegans, make them almost the only choice for studying the genetics of aging. The mouse, with its 2-year life span, is an exception to this rule; several genetic studies, including the analysis of short-lived mice, have been performed and used in an attempt to infer causal relationships. The mouse is the focus of a recent NIA initiative on mammalian models of aging. Recently human marker association" studies, where longevity is shown to be associated with defined regions of the human genome by characterizing molecular markers at certain candidate loci, have started to appear. Genetic approaches have been used also to identify the processes causing replicative senescence in human tissue culture. Two fundamentally distinct but overlapping questions have been the focus of genetic studies. What are the molecular mechanisms limiting life span? How does the process of evolution lead to aging and senescence? Although the answer to the latter question has been obtained to the satisfaction of most in the field, studies into the molecular basis continue. The details of the mechanisms leading to senescence and aging have not been forthcoming. Genetic approaches promise to fill this gap.
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[
1987]
Since the last review in this series [Johnson, 1985], many papers have appeared dealing directly with the aging process in both Caenorhabditis elegans and Turbatrix aceti. We will review this work and also briefly review other areas of C. elegans research that may impact on the study of aging. C. elegans has become a major biological model; four "News" articles in Science [Lewin, 1984a,b; Marx, 1984a,b] and inclusion as one of three developmental genetics models in a recent text [Wilkins, 1986] indicate its importance. Recent work has verified earlier results and has advanced progress toward new goals, such as routine molecular cloning. The aging studies reviewed here, together with new findings from other areas of C. elegans research, lay the groundwork for rapid advances in our understanding of aging in nematodes. Several areas of research in C. elegans have been reviewed recently: the genetic approach to understanding the cell lineage [Sternberg and Horvitz, 1984] and a brief summary of cell lineage mutants [Hedgecock, 1985]. The specification of neuronal development and neural connectivity has been a continuing theme in C. elegans research and reviews of these areas have also appeared [Chalfie, 1984; White, 1985]. A major genetic advance is the development of reliable, if not routine, mosaic analysis [Herman, 1984; Herman and Kari, 1985], which is useful for the genetic analysis of tissue-limited gene expression. Hodgkin [1985] reviews studies on a series of mutants involved in the specification of sex. These include her mutations that cause XO worms (normally males) to develop as hermaphrodites and tra mutations that change XX hermaphrodites into phenotypic males. The work on the structure and development of nematode muscle has been summarized by Waterston and Francis [1985]. A comprehensive review of aging research, containing useful reference material on potential biomarkers, has appeared [Johnson and Simpson, 1985], as well as a review including
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[
1987]
We describe the use of a nonspecific carboxylesterase as a biochemical marker for intestinal differentiation in the nematode C. elegans. In particular, we describe how esterase expression responds to inhibition of embryonic DNA synthesis by aphidicolin. Esterase expression requires a short period of DNA synthesis immediattely after the gut lineage is clonally established. However, the subsequent 2-3 rounds of DNA synthesis, which normally occur before esterase gene transcription, can be inhibited without effect. Thus esterase expression depends neither on reaching the normal DNA:cytoplasmic ration nor on counting the normal number of replication rounds.
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[
1989]
Transposable elements have recently been described in several species: Caenorhabditis elegans, Caenorhabditis briggsae, Ascaris lumbricoides, and Panagrellus redivivus. Because of the intense interest in C. elegans as an experimental organism for developmental genetic studies and the availability of sophisticated genetics, most is know about transposons in this species. This review focuses principally on Tc1 (Tc=transposon) of C. elegans, the best understood element in nematodes. Other elements in C. elegans and also elements in other species of nematodes will be briefly surveyed. The interested reader should also see two recent related reviews. The genome of C. elegans is 8 x 10(7) base pairs (bp) in extent, the smallest known for any metazoan. There are six chromosomes per haploid set, and about 83% of C. elegans DNA behaves as single-copy sequence in renaturation experiments. The repeated sequences are of several types, including functional genes, inverted or "foldback" sequences, and short repeated sequences of a few hundred nucleotides. The global arrangment of these short repeats is of the "short-period-interspersion" or "Xenopus" pattern. Some of the repetitive sequences consist of transposable elements, and at least five distinct families have been identified in C. elegans, Tc1 through Tc5. The sequence of one Tc1 element has been determined and shows that Tc1 resembles bacterial insertion sequence elements with terminal inverted repeats and a central open reading frame. The complete sequences for any members of the other transposon families have not been determined, but the data suggest that Tc2, Tc3, and Tc5 are also insertion sequence-like in structure and that Tc4 is foldbacklike in structure. No "retrotransposon-like" elements have been identified in C. elegans, although such elements have been described in A.
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[
1985]
Studies of aging in nematodes are based largely on the hope that there are some general mechanisms of aging which can be expeditiously revealed in simple multicellular organisms. Although differing greatly from mammals in size, body plan, and some organ systems, nematodes nontheless strongly resemble other metazoans at the cellular, subcellular, and biochemical levels. Moreover, nematodes do exhibit some rather widespread aging phenomena, such as nutritional prolongation of life span, accumulation of age pigments, and enzyme alterations, and their short life span, cellular simplicity, and genetic manipulability can be real advantages in studying the mechanisms underlying these phenomena.
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[
1992]
Nematodes are generally small animals that superficially resemble miniature earthworms in overall shape. Although the morphology of Caenorhabditis elegans is very simple, the establishment or maintenance of this shape involves a large number of genes. Mutant C. elegans strains have been isolated in which worms are short and fat, abnormally long and thin, twisted into a left or right helix, or covered with irregular lumps. This chapter deals with experiments and observations that suggest how the basic shape of the nematode is first established during embryogenesis and why certain genes may be essential for normal morphogenesis.
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[
1987]
To my knowledge, a theory of "developmentally programmed aging" has never been explicitly stated, although the notion that aging has some relationship to development has certainly been proposed many times. In the preceding chapter (36), Dr. Hayflick has made a brief description of the central idea of developmental programming within aging. In order to discuss relevant evidence in this chapter, I would like to propose the following, somewhat more specific and operational definition: The theory of developmentally programmed aging posits that aging involves events controlled in ways recognizably similar to those that operate during development. This definition is perhaps a little less extreme than it might have been, since it uses the phrase "aging involves events" rather than the phrase "aging is caused by events." However, I think it captures most of the usual connotations of "developmentally programmed aging," and it at least has the virtue of testability. Of course, to test the theory, as defined, requires evidence of several sorts. In particular, it requires (a) that we understand how some aging events are controlled, (b) that we understand how some developmental events are controlled, and (c) that we know how to recognize whether there is or is not similarity between the two. A central message of what follows is that we are really only at the beginning of being able to test this theory, although some lines of approach do appear
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[
Adv Exp Med Biol,
2010]
Neuropeptides are short sequences ofamino acids that function in all multicellular organisms to communicate information between cells. The first sequence ofa neuropeptide was reported in 1970' and the number of identified neuropeptides remained relatively small until the 1990s when the DNA sequence of multiple genomes revealed treasure troves ofinformation. Byblasting away at the genome, gene families, the sizes ofwhich were previously unknown, could now be determined. This information has led to an exponential increase in the number of putative neuropeptides and their respective gene families. The molecular biology age greatly benefited the neuropeptide field in the nematode Caenorhabditis elegans. Its genome was among the first to be sequenced and this allowed us the opportunity to screen the genome for neuropeptide genes. Initially, the screeningwas slow, as the Genefinder and BLAST programs had difficulty identifying small genes and peptides. However, as the bioinformatics programs improved, the extent of the neuropeptide gene families in C. elegans gradually emerged.