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[
Lecture Notes in Computer Science,
2008]
One of the most tractable organisms for the study of nervous systems is the nematode Caenorhabditis elegans, whose locomotion in particular has been the subject of a number of models. In this paper we present a first integrated neuro-mechanical model of forward locomotion. We find that a previous neural model is robust to the addition of a body with mechanical properties, and that the integrated model produces oscillations with a more realistic frequency and waveform than the neural model alone. We conclude that the body and environment are likely to be important components of the worms locomotion subsystem.
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[
1983]
Most multicellular eukaryotes posses a distinct group of germ-line cells that produces oocytes in one sex and sperm in the other. The production of adult germ cells appears to involve several developmental steps. First, during early embryogenesis, one or a few cells are committd to become germ precursor cells. Secondly, after a period of proliferation, some or all germ line descendants of the germ precursor cell leave the mitotic cell cycle and enter meiotic prophase. Thirdly, the meiotic germ cell matures as either a sperm or an oocyte. In this paper, I will review our knowledge of how each of these steps might be controlled in the small non-parasitic soil nematode, Caenorhabditis elegans.
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[
1985]
Myosins from slime molds to brain cells show a remarkable commonality of general molecular properties. These characteristics include two globular domains or heads that contain ATPase and actin-binding sites and the fibrous, coiled-coil a-helical rod that interacts with other molecules in assembly. Two heavy chains (m.w. 200,000) contribute to both heads, whereas two kinds of light chains bind to each head. In this paper, we consider striated muscles and their myosins. The phylogenetically distant nematode body-wall muscles and rabbit fast skeletal muscles produce myosin heavy chains, with about 47% of the amino acid sequences in the heads and 37% of the amino acids in the rod being identical (Karn et al. 1984). Myosin heavy chains are therefore highly conserved proteins. Contrasting with the phylogenetic conservation of myosin structure and sequence is the diversity of supramolecular arrangements of myosin assemblies in striated muscles, the so-called thick filaments. The lengths of thick filaments range from 1.55 um in vertebrates, 2-4 um in insect flight muscles, 10 um in the nematode to 40 um in certain mollusks. The average diameters of these filaments range from about 15 nm in vertebrates, 20 nm in insects, 25 nm in nematodes to 50-100 nm in some molluscan muscles. The surface arrangements of the myosin heads also vary in these different species. The lattice arrangements between thick filaments and the interdigitating, actin-containing thin filaments differ in terms of symmetry and thick:thin stoichiometry between these muscles. It appears likely that other protein components of these muscles interact with the very similar myosins to produce this structural diversity. The relatively subtle differences between myosin isoforms may also be important in these interactions. We define isoform in the case of myosin, for example, as a protein that is defined as a myosin by biochemical criteria but that can be distinguished on the basis of intrinsic molecular structure from another myosin within the same organism. In this paper, we describe experiments suggesting that two genetically different isoforms of myosin play distinct roles in concert with other proteins during the assembly of thick filaments in
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[
2003]
Since the publication of the first genetic research paper on Caenorhabditis elegans (C. elegans for short) in 1974, this microscopic, free-living nematode has become a popular model organism to study development, neurobiology, and other biological problems. The ability to do powerful genetics has been the most critical reason why studies using this organism have made enormous contributions to basic biology and medical science. Therefore, C. elegans genetics should be part of any modern genetic education. In this chapter, we describe some of the unique properties of C. elegans that makes it an exceptional organism for genetic and molecular biological research. Some important genetic tools and methodologies developed by C. elegans researchers will also be introduced. We aim to connect the fundamental principles of genetics as described in early chapters with practical applications of these principles in actual research. We have chosen a few genetic pathways and biological problems as examples for illustrating the logic behind the genetic analyses and for introducing some commonly practiced strategies and methods. We do not hesitate to introduce some of the most advanced and up-to-date methods and approaches, including those developed since the genome sequence was determined in 1998. We believe today's students can go right into the heart of present research after learning the basic principle of Genetics (see the early chapters of this book) and molecular biology. In fact, in many C. elegans laboratories, undergraduate students are doing a wide variety of experiments using the genetic techniques
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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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[
1979]
In many invertebrates, cell lineages are apparently invariant from individual to individual. A given precursor cell follows a specific pattern of cell divisions, and its descendants follow fates that correspond to their respective positions in the lineage tree. Such a reproducible sequence of events provides an excellent system for studying how cells come to pursue particular fates during development. We have been interested to know if a cell's fate is specified by factors intrinsic to the cell, or if it is influenced by interactions between the cell and its environment. C. elegans is a particularly suitable organism for lineage studies because it is transparent throughout its life cycle, and because it consists of relatively few cells. Furthermore, C. elegans is a favorable organism for genetics, so the control of cell lineages can be studied by characterizing mutations that are defective in known lineages. The cell lineages of C. elegans have been described in the embryo to the 182 cell stage and after hatching. Approximately 50 cells resume divisions post-embyronically. In the somatic tissues, the number of cells (or nuclei) is increased from about 550 to about 950 in hermaphrodites and to about 1025 in males. These post-embryonic lineages are essentially invariant from worm to worm. As the worm enlarges and matures sexually, cells (or nuclei) are added to previously existing tissues (hypodermis, muscle, gut, and nervous system), and structures necessary for reproduction are elaborated. The latter include a gonad in both sexes, a vulva in hermaphrodites, and a tail specialized for copulation in males. This paper summarizes the results of laser ablation experiments performed on cells in the post-embryonic lineages of C. elegans. In particular, we focus on those experiments that demonstrate a regulative capacity in the cells of this predominantly invariant system. The post-embyronic lineages have the practical advantage for these studies that they can be traced by direct observation of the cells as they divide and assume their final fate. The regulative response, therefore, can be described at a level of cellular detail that has not been possible in other deletion studies. Our aim in performing these experiments is to infer how cells are controlled during normal development from their behavior in
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[
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
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[
1977]
The soil nematode Caenorhabditis elegans was selected 11 years ago by Sydney Brenner as an experimental organism suitable for the isolation of many behavioral mutants and small enough for anatomical analysis of such mutants with the electron microscope. Two distinct goals motivated the initial studies of this organism: first, the hope that some of the mutants would have simple anatomical alterations that could be directly correlated with their behavioral defects, allowing the assignment of specific functions to specific neurons, and second, the hope that the detailed analysis of the kinds of alterations induced by individual mutations and the classes of cells affected by given mutations would reveal general features of the genetic program that specifies the development of the organism. Over the past 11 years the number of investigators working on C. elegans has increased to about 75 and is still growing. Nearly 3,000 different mutants have been isolated and different investigators are pursuing their effects on different cells. My own research is in the development of the nervous system. In particular, I would like to learn something about the workings of the complex black box that connects individual genes to the determination of the morphology of developing neurons. Are there gene products whose specific function is to determine the morphology of cells? If so, what are these gene products and how do they act in the developing cell? One would anticipate that mutations in such hypothetical genes would cause specific morphological alterations in cells. Because the morphology of a neuron determines its function, by selecting behavioral mutants altered in the function of the nervous system one might commonly find mutants that alter the morphology of neurons, and some of these might be in specific morphological genes. It is my hope that it will be possible to compare such mutants to the wild type in order to identify the defective gene products and thereby learn something about the role of normal gene products in determining the development of neurons. In this paper I will first summarize the results of several years' work on one specific class of mutants in the nematode, sensory mutants, work performed both in my laboratory and that of my colleagues Jim Lewis and Jonathan Hodgkin. Second, I will discuss frankly some of the difficulties and frustrations we have experienced in trying to interpret the effects of these specific mutants. Some of these difficulties illustrate problems endemic to genetic studies of development. Third, I will describe the more recent work performed in my labortory that is being directed toward genetic analysis of the structure and function of a