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

The C. elegans insulin/IGF-1 signaling (IIS) pathway connects nutrient levels to metabolism, growth, development, longevity, and behavior. This fundamental pathway is regulated by insulin-like peptide ligands that bind to the insulin/IGF-1 transmembrane receptor (IGFR) ortholog DAF-2. DAF-2/IGFR controls the activity of a conserved phosphoinositide 3-kinase (PI3K)/Akt kinase cascade, culminating in the regulation of a FoxO transcription factor, DAF-16, that governs most of the functions of this pathway. In light of the evolutionary conservation of the IIS pathway, its study in C. elegans is likely to shed light on its functions and regulation in higher organisms, including humans. Originally identified based on its role in the regulation of larval development and aging, IIS also controls a host of other biological processes. Here we review what is currently known about the biological functions and the molecular components of C. elegans IIS.

Wnt proteins are secreted lipid-modified glycoproteins that control many aspects of development in organisms ranging from sponges to vertebrates. Wnt proteins are also important regulators of C. elegans development, with functions in processes as diverse as cell fate specification, asymmetric cell division, cell migration and synapse formation. In this review, we will give an overview of what we currently know about the signaling mechanisms that mediate these different functions of Wnt.

Microfluidics has emerged as a set of powerful tools that have greatly advanced some areas of biological research, including research using C. elegans. The use of microfluidics has enabled many experiments that are otherwise impossible with conventional methods. Today there are many examples that demonstrate the main advantages of using microfluidics for C. elegans research, achieving precise environmental conditions and facilitating worm handling. Examples range from behavioral analysis under precise chemical or odor stimulation, locomotion studies in well-defined structural surroundings, and even long-term culture on chip. Moreover, microfluidics has enabled coupling worm handling and imaging thus facilitating genetic screens, optogenetic studies, and laser ablation experiments. In this article, we review some of the applications of microfluidics for C. elegans research and provide guides for the design, fabrication, and use of microfluidic devices for C. elegans research studies.

The ~100 MB genome of C. elegans codes for ~20,000 protein-coding genes many of which are required for the function of the nervous system, composed of 302 neurons in the adult hermaphrodite and of 383 neurons in the adult male. In addition to housekeeping genes, a differentiated neuron is thought to express many hundreds if not thousands of genes that define its functional properties. These genes code for ion channels, G-protein-coupled receptors, neurotransmitter-synthesizing enzymes, transporters and receptors, neuropeptides and their receptors, cell adhesion molecules, motor proteins, signaling molecules and many others. Collectively such genes have been referred to as "terminal differentiation genes" or "effector genes". The differential expression of distinct combinations of terminal differentiation genes define different neuron types. This paper provides a compendium of more than 2,800 putative terminal differentiation genes. One pervasive theme revealed by the analysis of many gene families is the nematode-specific expansions of many neuron function-related gene families, including, for example, many types of ion channel families, sensory receptors and neurotransmitter receptors. The gene lists provided here can serve multiple purposes. They can serve as quick reference guides for individual gene families or they can be used to mine large datasets (e.g., expression datasets) for genes with likely functions in the nervous system. They also serve as a starting point for future projects. For example, a comprehensive understanding of the regulation of the often complex expression patterns of these genes in the nervous system will eventually explain how nervous systems are built.

Receptor Tyrosine Kinase (RTK)-Ras-Extracellular signal-regulated kinase (ERK) signaling pathways control many aspects of C. elegans development and behavior. Studies in C. elegans helped elucidate the basic framework of the RTK-Ras-ERK pathway and continue to provide insights into its complex regulation, its biological roles, how it elicits cell-type appropriate responses, and how it interacts with other signaling pathways to do so. C. elegans studies have also revealed biological contexts in which alternative RTK- or Ras-dependent pathways are used instead of the canonical pathway.

Transforming Growth Factor-β (TGF-β) superfamily ligands regulate many aspects of cell identity, function, and survival in multicellular animals. Genes encoding five TGF-β family members are present in the genome of C. elegans. Two of the ligands, DBL-1 and DAF-7, signal through a canonical receptor-Smad signaling pathway; while a third ligand, UNC-129, interacts with a noncanonical signaling pathway. No function has yet been associated with the remaining two ligands. Here we summarize these signaling pathways and their biological functions.

The proper understanding and use of statistical tools are essential to the scientific enterprise. This is true both at the level of designing one's own experiments as well as for critically evaluating studies carried out by others. Unfortunately, many researchers who are otherwise rigorous and thoughtful in their scientific approach lack sufficient knowledge of this field. This methods chapter is written with such individuals in mind. Although the majority of examples are drawn from the field of Caenorhabditis elegans biology, the concepts and practical applications are also relevant to those who work in the disciplines of molecular genetics and cell and developmental biology. Our intent has been to limit theoretical considerations to a necessary minimum and to use common examples as illustrations for statistical analysis. Our chapter includes a description of basic terms and central concepts and also contains in-depth discussions on the analysis of means, proportions, ratios, probabilities, and correlations. We also address issues related to sample size, normality, outliers, and non-parametric approaches.