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[
1994]
The current interest in the nematode Caenorhabditis elegans began approximately 25 years ago when Sidney Brenner selected this species as the most suitable for studies of metazoan development and nervous system. The basis of this selection rested on the anatomical simplicity of nematodes, which nevertheless possess the major differentiated cell types of higher animals, and the tractability of C. elegans to the genetic approach. Over the past two decades or so, progress has been impressive: the cell lineage from egg to adult and the anatomy of the nervous system have been completely described, genetic investigations of numerous developmental problems are co-ordinated within a universally-agreed, systematic nomenclature, a physical map of the C. elegans genome is nearing completion and a project to sequence the entire genome is underway. Furthermore, the number of laboratories seeking to understand the mechanisms controlling animal development through genetic and molecular investigations of C. elegans is rising rapidly as the advantages of this organism become
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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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[
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
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[
2008]
Germline stem cells (GSCs) can generate haploid gametes, sperms or oocyte, which are responsible for transmitting genetic information from generation to generation. Because GSCs can be easily identified and gene functions can be readily manipulated in Drosophila and C. elegans, their niches were among the first to be functionally and anatomically defined. Genetic and cell biological studies in these systems have first shown that stem cell function is controlled by extracellular cues from the niche, and intrinsic genetic programs within the stem cells. Important progress has also recently been made in localizing GSCs in the mouse testis. Here I will review recent progress and compare the differences and commonalities of GSC niches from different systems. Since the studies on GSC niches in Drosophila and C. elegans have provided guiding principles for initial identification of niches in other systems, I hope that this review will provide some stimulating thoughts about niche structures and functions of adult stem cells in somatic systems.
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[
1983]
In the preparation of this review, I have made the basic assumption that the desire of the reader is to understand the biological basis of organismic aging. Given this premise, the organism of choice should be one that offers the most immediate hope of arriving at such an understanding. An ideal organism should have a short lifespan; be inexpensive to maintain; be experimentally malleable by a variety of techniques including molecular, morphological, genetic, and biological approaches; and be the object of study in a sufficient number of different laboratories to assure the accumulation of a critical mass of data. The nematode, Caenorhabditis elegans, admirably fulfills all of these basic requirememts. Researchers in the field of aging are faced with a large number of different theories which purport to explain the molecular basis of organismic aging. There are two major reasons for this proliferation of theoretical views. First, aging is an extremely complex phenomenon involving changes in a number of different physiological systems; these physiological changes are often detected, but proof that any one of the changes is responsible for aging is lacking. Second, the focus of a great deal of the research in the field has not been so much on understanding the biological basis of the entire aging process as on understanding one or another of the consequences of this process, particularly in humans and other mammals. The mammalian model systems may often be quite inappropriate for addressing the more basic, long-term questions about the
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[
Methods Cell Biol,
1995]
Although Caenorhabditis elegans was originally chosen as a model organism for cell biology with serial section electron microscopy (EM) methods in mind, these methods have remained a daunting challenge. There is an apocryphal story that Nichol Thomson originally advised Sydney Brenner that C. elegans was unsuitable for electron microscopy and that Brenner should choose another species. Other experienced microscopists have probably shared similar dark thoughts from time to time. Nonetheless, the worm's very small size, simple organization, and cablelike nervous system have permitted Brenner's colleagues to characterize every cell and cell contact in the wild-type animal, potentiating the genetic characterization of cellular development in remarkable detail. We attempt to provide an adequate background for anyone to initiate EM studies of C. elegans. Two decades ago, as the first of Brenner's postdoctoral fellows left his laboratory to establish new worm laboratories, it was standard practice to include an EM component in their studies. Their combined efforts to characterize the adult animal's cell types and the essential steps in its development helped to erect a lovely scaffold of key manuscripts, capped by the description of the "Mind of the Worm" in some 600 micrographs and 175 drawings. Many of these works required technical heroics or suffered long delays before publication. Most people later chose to leave electron microscopy behind in pursuit of molecular quarry. The fruits of their molecular and genetic studies should soon stimulate a renewed flowering of electron microscopy. We hope to smooth your entry or reentry into these techniques. We also summarize our methods for three-dimensional (3D) image reconstruction, based largely on film techniques introduced by John White and Randle Ware. Digital imaging techniques seem poised to make 3D reconstruction more accessible, and may simplify the exchange of morphological data between laboratories. We discuss several computer systems that the C. elegans community could adopt for high-resolution studies of structure and function. In addition, we briefly cover several specialized specimen preparation techniques for electron microscopy, including freeze fracture and electron microscopic immunocytochemistry.