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Methods Cell Biol,
1995]
Geneticists like to point out that the ultimate test of a proposed function for a gene and its encoded product (or products) in a living organism involves making a mutant and analyzing its phenotype. This is the goal of reverse genetics: a gene is cloned and sequenced, its transcripts and protein coding sequence are analyzed, and a function may be proposed; one must then introduce a mutation in the gene in a living organism to see what the functional consequences are. The analysis of genetic mosaics takes this philosophy a step further. In mosaics, some cells of an individual are genotypically mutant and other cells are genotypically wild type. One then asks what the phenotypic consequences are for the living organism. This is not the same as asking what cells transcribe the gene or in what cells the protein product of the gene is to be found, but rather it is asking in what cells the wild-type gene is needed for a given function...
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Cell,
2002]
Inherited mutations in BRCA1 or BRCA2 predispose to breast, ovarian, and other cancers. Their ubiquitously expressed protein products are implicated in processes fundamental to all cells, including DNA repair and recombination, checkpoint control of cell cycle, and transcription. Here, I examine what is known about the biological functions of the BRCA proteins and ask how their disruption can induce susceptibility to specific types of cancer.
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Trends Biochem Sci,
1984]
For this 100th issue of TIBS, we were asked to look back at our subjects about eight years to when the journal first appeared and to discuss the important developments since that time. I found myself looking further back and I beg the reader's indulgence for some history that goes back some 21 years to the origins of our work on Caenorhabditis elegans.
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Results Probl Cell Differ,
1987]
How is a germ cell instructed to differentiate as a sperm or oocyte? This is essentially a question of sex determination asked at the cellular level. Sex determination in the germ line has been elusive to experimentation in both Drosophila and in mice. However, in the nematode, Caenorhabditis elegans, control over the choice between spermatogenesis and oogenesis has proven to be particularly accessible to genetic analysis. In this chapter, we review our current knowledge of the mechanisms in C. elegans that influence this decision.
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Nat Methods,
2013]
In this Historical Perspective, we ask what information is needed beyond connectivity diagrams to understand the function of nervous systems. Informed by invertebrate circuits whose connectivities are known, we highlight the importance of neuronal dynamics and neuromodulation, and the existence of parallel circuits. The vertebrate retina has these features in common with invertebrate circuits, suggesting that they are general across animals. Comparisons across these systems suggest approaches to study the functional organization of large circuits based on existing knowledge of small circuits.
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Methods Cell Biol,
1995]
One way to study cell function is to eliminate the cell and observe subsequent developmental or behavioral abnormalities in the animal. In Caenorhabditis elegans, this is usually accomplished by killing individual cells or groups of cells with a laser microbeam. Laser killing has been used to determine the functions of many mature cell types, including neurons involved in locomotion, feeding, mechanosensation, and chemosensation. These studies have been practical because only a few cell types appear to be absolutely required for viability. Laser ablation can also be sued to ask how cells interact during development. Signaling and inductive interactions between cells can be examined by removing one cell and observing the development of the remaining cells...
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Mech Ageing Dev,
2002]
Studying the phenomenon of aging is interesting for many reasons including because one would like to be able to extend the life span of people. However, we believe that the aging process instill so poorly understood that it remains unclear what exactly we will have to learn about it in order to understand it. Strehler, and others, have tried to ask questions about aging at several different levels at which biological systems can be studied (Strehler, 1985, 1995). Here, we will first discuss a number of nested viewpoints on aging, and then focus on some recent studies, particularly in Caenorhabditis elegans, in which several lines of investigation intersect: the study of long-lived mutants, the properties of the germline, and the biology of telomeres.
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Cell,
2000]
Current understanding of the way in which embryonic polarity is established relies heavily on studies of maternal effect lethal mutants in D. melanogaster and C. elegans. Although the analysis in worms began in earnest about a decade after the explosion of information from flies, we now know enough about both systems to make comparisons meaningful, and to ask whether there are conserved mechanisms used for establishing embryonic polarity. Thus far, the single common feature is translational repression, which has been shown to localize important fate regulators in both systems. Now, however, in this issue of Cell, Shulman and colleagues report an analysis in D. melanogaster of the first molecule to play an important and perhaps conserved role in both animals, PAR-1.
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Cold Spring Harb Perspect Biol,
2010]
RNA interference (RNAi) provides a powerful reverse genetics approach to analyze gene functions both in tissue culture and in vivo. Because of its widespread applicability and effectiveness it has become an essential part of the tool box kits of model organisms such as Caenorhabditis elegans, Drosophila, and the mouse. In addition, the use of RNAi in animals in which genetic tools are either poorly developed or nonexistent enables a myriad of fundamental questions to be asked. Here, we review the methods and applications of in vivo RNAi to characterize gene functions in model organisms and discuss their impact to the study of developmental as well as evolutionary questions. Further, we discuss the applications of RNAi technologies to crop improvement, pest control and RNAi therapeutics, thus providing an appreciation of the potential for phenomenal applications of RNAi to agriculture and medicine.
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J Biosci,
2009]
Understanding how the environment impacts development is of central interest in developmental and evolutionary biology. On the one hand, we would like to understand how the environment induces phenotypic changes (the study of phenotypic plasticity). On the other hand, we may ask how a development system maintains a stable and precise phenotypic output despite the presence of environmental variation. We study such developmental robustness to environmental variation using vulval cell fate patterning in the nematode Caenorhabditis elegans as a study system. Here we review both mechanistic and evolutionary aspects of these studies, focusing on recently obtained experimental results. First, we present evidence indicating that vulval formation is under stabilizing selection. Second, we discuss quantitative data on the precision and variability in the output of the vulval developmental system in different environments and different genetic backgrounds. Third, we illustrate how environmental and genetic variation modulate the cellular and molecular processes underlying the formation of the vulva. Fourth, we discuss the evolutionary significance of environmental sensitivity of this developmental system.