WormBook : the online review of C. elegans biology最新文献

A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) Caenorhabditis elegans as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on C. elegans has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host-parasite interactions, and evolution. C. elegans has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in C. elegans research. Key to studying C. elegans has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make C. elegans useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues.

Nuclear receptors are transcription factors that often respond to small molecule metabolites and fat-soluble compounds to regulate gene expression. They broadly govern development, reproduction, metabolism, and homeostasis in diverse metazoan species and their dysregulation is associated with numerous diseases. Work in C. elegans has shed light on the seminal role of nuclear receptors in life history regulation, stem cell progression, developmental timing, cell fate specification, nutrient sensing, metabolism, and longevity. Here we highlight recent advances on the best-studied nuclear receptors in the worm, and how they illuminate metazoan biology.

Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. The vast majority of these are of a type where the genes in the cluster are ~100 bp apart and the pre-mRNA is processed by 3' end formation accompanied by trans-splicing. A spliced leader, SL2, is specialized for operon processing. Here we summarize current knowledge on several variations on this theme including: (1) hybrid operons, which have additional promoters between genes; (2) operons with exceptionally long (> 1 kb) intercistronic regions; (3) operons with a second 3' end formation site close to the trans-splice site; (4) alternative operons, in which the exons are sometimes spliced as a single gene and sometimes as two genes; (5) SL1-type operons, which use SL1 instead of SL2 to trans-splice and in which there is no intercistronic space; (6) operons that make dicistronic mRNAs; and (7) non-operon gene clusters, in which either two genes use a single exon as the 3' end of one and the 5' end of the next, or the 3' UTR of one gene serves as the outron of the next. Each of these variations is relatively infrequent, but together they show a remarkable variety of tight-linkage gene arrangements in the C. elegans genome.

Polarity establishment, asymmetric division, and acquisition of cell fates are critical steps during early development. In this review, we discuss processes that set up the embryonic axes, with an emphasis on polarity establishment and asymmetric division. We begin with the first asymmetric division in the C. elegans embryo, where symmetry is broken by the local inactivation of actomyosin cortical contractility. This contributes to establishing a polarized distribution of PAR proteins and associated components on the cell cortex along the longitudinal embryonic axis, which becomes the anterior-posterior (AP) axis. Thereafter, AP polarity is maintained through reciprocal negative interactions between the anterior and posterior cortical domains. We then review the mechanisms that ensure proper positioning of the centrosomes and the mitotic spindle in the one-cell embryo by exerting pulling forces on astral microtubules. We explain how a ternary complex comprised of Gα (GOA-1/GPA-16), GPR-1/GPR-2, and LIN-5 is essential for anchoring the motor protein dynein to the cell cortex, where it is thought to exert pulling forces on depolymerizing astral microtubules. We proceed by providing an overview of cell cycle asynchrony in two-cell embryos, as well as the cell signaling and spindle positioning events that underly the subsequent asymmetric divisions, which establish the dorsal-ventral and left-right axes. We then discuss how AP polarity ensures the unequal segregation of cell fate regulators via the cytoplasmic proteins MEX-5/MEX-6 and other polarity mediators, before ending with an overview of how the fates of the early blastomeres are specified by these processes.

The facilitated movement of ions across cell membranes can be characterized as occurring through active (ATP-dependent), secondary active (coupled), or passive transport processes. Each of these processes is mediated by a diverse group of membrane proteins. Over the past fifteen years, studies of membrane transport in C. elegans have benefited from the fact that worms are anatomically simple, easily and economically cultured, and genetically tractable. These experimental advantages have been instrumental in defining how membrane transport processes contribute to whole organism physiology. The focus of this review is to survey the recent advances in our understanding of membrane transport that have arisen from integrative physiological approaches in the nematode C. elegans.

Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.

A distinctive feature of polarized epithelial cells is their specialized junctions, which contribute to cell integrity and provide platforms to orchestrate cell shape changes. This chapter discusses the composition, assembly and remodeling of C. elegans cell-cell (CeAJ) and hemidesmosome-like cell-extracellular matrix junctions (CeHD), proteins that anchor the cytoskeleton, and mechanisms involved in establishing epithelial polarity. Major recent progress in this area has come from the analysis of mechanisms that maintain cell polarity, which involve lipids and trafficking, and on the impact of mechanical forces on junction remodeling. This chapter focuses on cellular, rather than developmental, aspects of epithelial cells.

In the early stage of the C. elegans sequencing project, the ab initio gene prediction program Genefinder was used to find protein-coding genes. Subsequently, protein-coding genes structures have been actively curated by WormBase using evidence from all available data sources. Most coding loci were identified by the Genefinder program, but the process of gene curation results in a continual refinement of the details of gene structure, involving the correction and confirmation of intron splice sites, the addition of alternate splicing forms, the merging and splitting of incorrect predictions, and the creation and extension of 5' and 3' ends. The development of new technologies results in the availability of further data sources, and these are incorporated into the evidence used to support the curated structures. Non-coding genes are more difficult to curate using this methodology, and so the structures for most of these have been imported from the literature or from specialist databases of ncRNA data. This article describes the structure and curation of transcribed regions of genes.

During the first stage of larval development, the Q neuroblasts and their descendants migrate to well-defined positions along the anteroposterior body axis, where they differentiate into sensory neurons and interneurons. The two Q neuroblasts are initially present at similar positions on the left and right lateral side, but this symmetry is broken when the Q neuroblast on the left side (QL) polarizes towards the posterior and the Q neuroblast on the right side (QR) towards the anterior. This left-right asymmetry is maintained when the descendants of the two Q neuroblasts migrate to their final positions in the posterior and anterior. The mechanisms that establish this asymmetry and control the migration of the Q descendants along the anteroposterior axis are surprisingly complex and include interplay between Wnt signaling pathways, homeotic genes, and the basic cell migration and polarity machinery. Here, we will give an overview of what is currently known about the mechanisms that mediate and control the development and migration of the Q neuroblasts and their descendants.