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Genetic analysis of C. elegans development has focused on developmental events that take place after hatching, during postembryonic development. After hatching with 558 cells, about 10% of these are blast cells that undergo further cell divisions (Fig. 1) to generate a total of 959 neurons, muscles, intestinal and hypodermal cells in the hermaphrodite and 1031 cells in the male. Like embryonic development (se Edgar, Chap. 19 this Vol.), the pattern of cell division and differentiation during C. elegans postembryonic development is nearly invariant and has been completely described. The cell lineage of wild-type, mutant, or laser-ablated animals can be determined by direct observation of development using Normarski optics. Because most cells during C. elegans postembryonic development generate unique patterns of descendents (though symmetries in the lineage exist), the cell lineage produced by a particular blast cell during development is a signature of that cell's identity. Any changes in cell identity, induce, for example, by laser ablation or neighboring cells or by mutation, can be recognized by a change in the lineage produced by that cell. By laser ablation, it has been shown that in many cases, that patterns of cell lineage executed by particular cells do not depend on their neighbors and instead reflect some intrinsic developmental program. On the other hand, the lineages of particular blast cells, for example, those that generate the hermaphrodite vulva, have been shown by laser ablation experiments to depend on interactions with their neighbors. Thus the pattern of cell divisions and differentiations that normally occur during C. elegans development depends on the ancestry of cells in some cases on their neighbors or positional signals in other cases. Two major goals of developmental genetic analysis in C. elegans have been to explain how genes couple cell lineage information to cell identity and to explain how genes control and mediate cell-cell interactions. As described below, this analysis has revealed molecular mechanisms for the generation of lineage asymmetry and for intercellular signaling that are general to perhaps all metazoans.
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[
1987]
We describe an experimental system in which to study gene-specific segregation mechanisms during early development of C. elegans. A non-specific esterase, of unknown physiological function, has convenient properties as a biochemical marker of differentiation: expression is localized to the gut lineage, is due to transcription during zygotic development and is lineage autonomous. The timing of esterase expression does not depend either on the normal number of rounds of cytokinesis or on the normal number of rounds of DNA replication; thus some other clock mechanism must be invoked. We descrbe experiments suggesting that DNA strands donated by the sperm do not co-segregate during development of the next generation.
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[
Modern Cell Biology,
1994]
During the development of any multicellular organism, the behavior of any given cell can be influenced in two ways: by its ancestry, i.e., by the particular pattern of determinants it inherits (lineal programming); or by its environment, i.e., the signals it receives from other cells. In C. elegans, the relative importance of these two factors for the development of any given cell can be examined with an unusually high degree of precision. There are a number of reasons for this, but perhaps the most important is that the cell lineage, the particular pattern of cell divisions and differentiations that occur in development, is known, and is largely the same from animal to animal. Alterations in the lineage, therefore, can be understood in terms of altered developmental decisions of
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[
1991]
During the development of the nematode, Caenorhabditis elegans, cell fates are determined via a combination of cell-autonomous and cell-nonautonomous mechanisms. The latter, regulative phenomena, require the existence of one or more intercellular signaling pathways. In this review, we consider the function of two genes,
lin-12 (lineage abnormal) and
glp-1 (germ line proliferation defective), that are required for intercellular signaling during nematode development.
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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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[
1984]
Developmental fates of blastomeres in early C. elegans embryos appear to be governed by internally segregating, cell-autonomous determinants. To ascertain whether previously described gut-lineage dterminants are nuclear or cytoplasmic, laser microsurgery was used to show that exposing the nucleus of a non-gut-precursor cell to gut-precursor cytoplasm can cause the progeny of the resulting hybrid cell to express gut-specific differentiation markers, supporting the view that the determinants are cytoplasmic. In attempts to obtain molecular probes for such determinants, a library of monoclonal antibodies to early embryonic antigens was generated and screened by immunofluorescence microscopy for antibodies reacting with lineage-specific components. Three of the antibodies react with cytoplasmic granules (P granules) that segregate specifically with the germ line in early cleavages and are found uniquely in germ-line cells throughout the life cycle. Experiments on unfertilized eggs, on mutant embryos with defects in early cleavage, and on normal embryos treated with various cytoskeletal inhibitors indicate that P-granule segregation depends upon fertilization and requires the function of actin microfilaments, but is independent of spindle and microtubule functions. Work on the biochemical nature and function of the P granules is in progress.
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[
WormBook,
2008]
Germline apoptosis shares with somatic apoptosis a reliance on key components of the core apoptotic machinery, including CED-3 and CED-4. However, germline apoptosis differs from somatic apoptosis in its regulation. Whereas somatic apoptosis is developmentally programmed by cell lineage, germline apoptosis occurs as part of an oogenesis program. One category of germline apoptosis, dubbed "physiological" germline apoptosis, reduces the number of cells that complete oogenesis, and is independent of the BH3-only apoptosis effecter EGL-1. A second category, termed "stress-induced" germline apoptosis, is triggered by a genomic integrity checkpoint. Some mechanisms that are monitored by this DNA-damage checkpoint are also involved in germ cell "immortality," or preservation of a continuous germ cell lineage over successive generations. In addition, exposure to certain environmental insults or pathogens induces germ cell apoptosis. Here we will review the mechanisms that control each of the pathways leading to germ cell apoptosis and discuss their functional significance. Germline apoptosis is an integral part of oogenesis in many animals, including humans. Because many of the regulators of C. elegans germline apoptosis are conserved, we suggest that this nematode provides a valuable model for understanding controls of germline apoptosis more broadly.
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[
WormBook,
2007]
The intestine is one of the major organs in C. elegans and is largely responsible for food digestion and assimilation as well as the synthesis and storage of macromolecules. In addition, the intestine is emerging as a powerful experimental system in which to study such universal biological phenomena as vesicular trafficking, biochemical clocks, stress responses and aging. The present chapter describes some of these many and varied properties of the C. elegans intestine: the embryonic cell lineage, intestine morphogenesis, structure and physiology of the intestinal cell and, finally, the transcription factor network controlling intestine development and function.
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[
1987]
Mutations in genes that control developmental patterns undoubtedly underlie evolutionary change in development. The elucidation of the precise genetic basis of evolutionary change requires the identification and genetic analysis of key genes that control normal developmental patterns of an organism ("developmental control genes"), the analysis of the precise nature of developmental differences between that organism and its related species, and the determination of what changes in these developmental control genes actually cause the observed evolutionary developmental differences. Nematodes offer an excellent opportunity to study the roles of developmental control genes in evolutionary change. The simple anatomy and rapid life cycle of the nematode Caenorhabditis elegans has allowed a detailed analysis of its wild-type development. As a result, the complete cell lineage of C. elegans has been elucidated. This lineage is nearly invariant in the wild type; each cell is formed after a defined lineage history and at a specific time during development. Thus, the developmental defects of mutants can be accurately determined at the level of the fates expressed by specific cells at specific times in development. Through genetic analyses of C. elegans developmental mutants, genes have been identified that play crucial roles in specifying and expressing the normal developmental program. If these genes code for developmental control processes common to different nematode species, then mutations of these genes might underlie interspecific developmental change. Other nematode species can be isolated from the wild and cultured in the laboratory with ease. The relatively simple cellular anatomy of nematodes allows the direct comparison of cell lineages between different species on the level of individual cells and cell divisions. If genes affecting development in C. elegans play evolutionary roles, then developmental differences between species should emerge that parallel, or even are identical to, mutationally induced changes in C. elegans. It should eventually be possible to test directly which genes are responsible for certain evolutionary differences in development by altering
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Caenorhabditis elegans is a free-living soil nematode, about 1 mm in length, that is found around the world. It is currently a common laboratory model for many aspects of cellular, developmental, and molecular biology. Its popularity comes from its transparency (allowing all nuclei to be followed in living animals at all stages of development), its anatomical simplicity (1000 cells), its small genome (100 Mbp), an invariant somatic cell lineage, ease of laboratory culture, rapid generation time, and a mode of reproduction which facilitates classical genetic analysis. An interested beginner needs only a petri plate, some Escherichia coli, and a stereo dissecting microscope to begin study of this fascinating creature.