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

The nematode cuticle is an extremely flexible and resilient exoskeleton that permits locomotion via attachment to muscle, confers environmental protection and allows growth by molting. It is synthesised five times, once in the embryo and subsequently at the end of each larval stage prior to molting. It is a highly structured extra-cellular matrix (ECM), composed predominantly of cross-linked collagens, additional insoluble proteins termed cuticlins, associated glycoproteins and lipids. The cuticle collagens are encoded by a large gene family that are subject to strict patterns of temporal regulation. Cuticle collagen biosynthesis involves numerous co- and post-translational modification, processing, secretion and cross-linking steps that in turn are catalysed by specific enzymes and chaperones. Mutations in individual collagen genes and their biosynthetic pathway components can result in a range of defects from abnormal morphology (dumpy and blister) to embryonic and larval death, confirming an essential role for this structure and highlighting its potential as an ECM experimental model system.

As in all living organisms, survival in C. elegans requires adequate management of energy supplies. Genetic screens have revealed that C. elegans fat regulation involves a complex network of genes with known or likely functions in food sensation, neuroendocrine signaling, uptake, transport, storage and utilization of fats. Core fat and sugar metabolic pathways are conserved in C. elegans. Flux through these pathways is modulated by cellular energy sensors that operate via transcriptional and translational regulatory mechanisms. In turn, neuroendocrine mechanisms couple sensory and metabolic pathways while neuromodulatory pathways influence both metabolic and food seeking/consumption pathways. The shared ancestry of C. elegans and mammalian fat regulatory pathways extends to developmental programs that underlie fat storage capacity, despite lack of dedicated adipocytes, and genes whose human homologs are implicated in obesity. This suggests that many of the newly identified C. elegans fat regulatory pathways play similar roles in mammals. C. elegans is ideally suited for the integrated study of mechanisms that operate in multiple tissues and elicit feedback responses that affect processes as diverse as metabolism and behavior.

The non-motile cilium, once believed to be a vestigial cellular structure, is now increasingly associated with the ability of a wide variety of cells and organisms to sense their chemical and physical environments. With its limited number of sensory cilia and diverse behavioral repertoire, C. elegans has emerged as a powerful experimental system for studying how cilia are formed, function, and ultimately modulate complex behaviors. Here, we discuss the biogenesis, distribution, structures, composition and general functions of C. elegans cilia. We also briefly highlight how C. elegans is being used to provide molecular insights into various human ciliopathies, including Polycystic Kidney Disease and Bardet-Biedl Syndrome.

Sexual identity is one of a few basic parameters that specify how development should proceed. Although sex determination has profound effects on many tissues, its most ancient and fundamental role is ensuring that some germ cells become sperm, and others become oocytes or eggs. Spermatocytes and oocytes are usually produced in male and female animals, respectively, but C. elegans is uniquely suitable for studying the control of these cell fates because both types of cells are made from a common pool of progenitors in XX hermaphrodites. Extensive genetic and molecular studies have shown that the sexual fate of germ cells in C. elegans is controlled by the same genes that regulate sexual identity in other parts of the animal. However, this regulatory pathway has additional features that are unique to the germ line. First, several genes, like the three fogs, act only in germ cells. Second, the three fem genes act in concert with targets of tra-1 to control germ cell fates, but do not act this way in the soma. Third, translational repression of tra-2 is essential for hermaphrodite spermatogenesis. Fourth, translational repression of fem-3 is needed for oogenesis. In this review, we present genetic and molecular models for how these processes work, and summarize the evidence upon which they are built.

Heterorhabditis bacteriophora is an entomopathogenic nematode (EPN) mutually associated with the enteric bacterium, Photorhabdus luminescens, used globally for the biological control of insects. Much of the previous research concerning H. bacteriophora has dealt with applied aspects related to biological control. However, H. bacteriophora is an excellent model to investigate fundamental processes such as parasitism and mutualism in addition to its comparative value to Caenorhabditis elegans. In June 2005, H. bacteriophora was targeted by NHGRI for a high quality genome sequence. This chapter summarizes the biology of H. bacteriophora in common and distinct from C. elegans, as well as the status of the genome project.

Four biogenic amines: octopamine, tyramine, dopamine and serotonin act in C. elegans to modulate behavior in response to changing environmental cues. These neurotransmitters act at both neurons and muscles to affect egg laying, pharyngeal pumping, locomotion and learning. A variety of experimental approaches including genetic, imaging, biochemical and pharmacological analyses have been used to identify the enzymes and cells that make and release the amines and the cells and receptors that bind them. Dopamine and serotonin act through receptors and downstream signaling mechanisms similar to those that operate in the mammalian brain suggesting that C. elegans will provide a valuable model for understanding biogenic amine signaling in the brain.

Because of their free-living life cycle alternatives, Strongyloides and related nematode parasites may represent the best models for translating C. elegans science to the study of nematode parasitism. S. stercoralis, a significant pathogen of humans, can be maintained in laboratory dogs and gerbils. Biosafety precautions necessary for work with S. stercoralis, though unfamiliar to many C. elegans researchers, are straightforward and easily accomplished. Although specialized methods are necessary for large-scale culture of the free-living stages of S. stercoralis, small-scale cultures for experimental purposes may be undertaken using minor modifications of standard C. elegans methods. Similarly, the morphological similarities between C. elegans and the free-living stages of S. stercoralis allow investigational methods such as laser cell ablation and DNA transformation by gonadal microinjection to be easily adapted from C. elegans to S. stercoralis. Comparative studies employing these methods have yielded new insights into the neuronal control of the infective process in parasites and its similarity to regulation of dauer development in C. elegans. Furthermore, we have developed a practical method for transient transformation of S. stercoralis with vector constructs having various tissue- and cell-specific expression patterns and have assembled these into a modular vector kit for distribution to the community.

Great inroads into the understanding of aging have been made using C. elegans as a model system. Several genes have been identified that, when mutated, can extend lifespan. Yet, much about aging remains a mystery, and new technologies that allow the simultaneous assay of expression levels of thousands of genes have been applied to the question of how and why aging might occur. With correct experimental design and statistical analysis, differential gene expression between two or more populations can be obtained with high confidence. The ability to survey the entire genome in an unbiased way is a great asset for the study of complex biological phenomena such as aging. Aging undoubtedly involves changes in multiple genes involved in multiple processes, some of which may not yet be known. Gene expression profiling of wild type aging, and of strains with increased life spans, has provided some insight into potential mechanisms, and more can be expected in the future.

Acetylcholine is the major excitatory neurotransmitter at nematode neuromuscular junctions, and more than a third of the cells in the C. elegans nervous system release acetylcholine. Through a combination of forward genetics, drug-resistance selections, and genomic analysis, mutants have been identified for all of the steps specifically required for cholinergic function. These include two enzymes, two transporters, and a bewildering assortment of receptors. Cholinergic transmission is involved, directly or indirectly, in many C. elegans behaviors, including locomotion, egg laying, feeding, and male mating.

The C. elegans foregut (pharynx) has emerged as a powerful system to study organ formation during embryogenesis. Here I review recent advances regarding cell-fate specification and epithelial morphogenesis during pharynx development. Maternally-supplied gene products function prior to gastrulation to establish pluripotent blastomeres. As gastrulation gets under way, pharyngeal precursors become committed to pharyngeal fate in a process that requires PHA-4/FoxA and the Tbox transcription factors TBX-2, TBX-35, TBX-37 and TBX-38. Subsequent waves of gene expression depend on the affinity of PHA-4 for its target promoters, coupled with combinatorial strategies such as feed-forward and positive-feedback loops. During later embryogenesis, pharyngeal precursors undergo reorganization and a mesenchymal-to-epithelial transition to form the linear gut tube. Surprisingly, epithelium formation does not depend on cadherins, catenins or integrins. Rather, the kinesin ZEN-4/MKLP1 and CYK-4/RhoGAP are critical to establish the apical domain during epithelial polarization. Finally, I discuss similarities and differences between the nematode pharynx and the vertebrate heart.