秀丽线虫:低氧应答研究的模式生物

低氧能够引起秀丽线虫发生相应的生理和行为学变化,并可保护机体免受缺氧损伤.秀丽线虫的低氧诱导因子(HIF-1)的恒定性调控通路和人类的相应通路之间具有高度保守性,因此秀丽线虫也已成为研究低氧应答调控通路进化保守性的重要工具之一.阐明秀丽线虫的低氧应答机制将为了解人类低氧相关疾病的发病机制提供有价值的线索.     

Roles of MicroRNAs in the Caenorhabditis elegans Nervous System

The first microRNA was discovered in Caenorhabditis elegans in 1993, and since then, thousands of microRNAs have been identified from almost all eukaryotic organisms examined. MicroRNAs function in many biological events such as cell fate determination, metabolism, apoptosis, and carcinogenesis. So far, more than 250 microRNAs have been identified in C. elegans; however, functions for most of these microRNAs are still unknown. A small number of C. elegans microRNAs are associated with known physiological roles such as developmental timing, cell differentiation, stress response, and longevity. In this review, we summarize known roles of microRNAs in neuronal differentiation and function of C. elegans, and discuss interesting perspectives for future studies.     

Interactions between Caenorhabditis elegans individuals during chemotactic response

The chemotactic response of the nematode Caenorhabditis elegans is known to be affected by the population density on an assay plate, suggesting the existence of interactions between individual animals. To clarify the interactions between individuals during chemotaxis, we investigated the effect of population density at an attractant area on the chemotactic response to water-soluble sodium acetate and odorant diacetyl using wild-type N2 animals and daf-22 (m130) mutants, which have defective pheromone secretion but can sense pheromone. The chemotaxis index of N2 animals at 90 min of the assay negatively correlated with the number of animals on the assay plate regardless of the type of attractant used (p<0.01). On the other hand, there was no significant difference in the chemotaxis indices of daf-22 (m130) mutants for either of the attractants between the low-and high-population groups. When daf-22 (m130) mutants of a high population density were placed at the attractant location in advance, the chemotaxis index of N2 animals was almost the same as that in the control assay in which no animals were placed at the attractant location in advance. When N2 animals of a high population density were placed at the attractant location in advance, the chemotaxis indices of N2 animals and daf-22 (m130) mutants were significantly smaller than those obtained in the control assay (p<0.05). In the absence of an attractant, we observed a decline in the fraction of animals in the neighborhood of N2 animals of a high population density, although the nematodes were not influenced by daf-22 (m130) mutants of a high population density. These results suggest that the attraction of nematodes to chemicals is inhibited by an increase in the concentration of the pheromone generated by N2 animals at the attractant location.     

Roles of MAP kinase cascades in Caenorhabditis elegans

Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that are activated by diverse stimuli such as growth factors, cytokines, neurotransmitters and various cellular stresses. MAPK cascades are generally present as three-component modules, consisting of MAPKKK, MAPKK and MAPK. The precise molecular mechanisms by which these MAPK cascades transmit signals is an area of intense research, and our evolving understanding of these signal cascades has been facilitated in great part by genetic analyses in model organisms. One organism that has been commonly used for genetic manipulation and physiological characterization is the nematode Caenorhabditis elegans. Genes sequenced in the C. elegans genome project have furthered the identification of components involved in several MAPK pathways. Genetic and biochemical studies on these components have shed light on the physiological roles of MAPK cascades in the control of cell fate decision, neuronal function and immunity in C. elegans.     

Checkpoint silencing during the DNA damage response in Caenorhabditis elegans embryos

In most cells, the DNA damage checkpoint delays cell division when replication is stalled by DNA damage. In early Caenorhabditis elegans embryos, however, the checkpoint responds to developmental signals that control the timing of cell division, and checkpoint activation by nondevelopmental inputs disrupts cell cycle timing and causes embryonic lethality. Given this sensitivity to inappropriate checkpoint activation, we were interested in how embryos respond to DNA damage. We demonstrate that the checkpoint response to DNA damage is actively silenced in embryos but not in the germ line. Silencing requires rad-2, gei-17, and the polh-1 translesion DNA polymerase, which suppress replication fork stalling and thereby eliminate the checkpoint-activating signal. These results explain how checkpoint activation is restricted to developmental signals during embryogenesis and insulated from DNA damage. They also show that checkpoint activation is not an obligatory response to DNA damage and that pathways exist to bypass the checkpoint when survival depends on uninterrupted progression through the cell cycle.     

Roles for two partially redundant alpha-tubulins during mitosis in early Caenorhabditis elegans embryos

The Caenorhabditis elegans genome encodes multiple isotypes of alpha-tubulin and beta-tubulin. Roles for a number of these tubulins in neuronal development have been described, but less is known about the isoforms that function during early embryonic development. Microtubules are required for multiple events after fertilization produces a one-cell zygote in C. elegans, including pronuclear migration, mitotic spindle assembly and function, and proper spindle positioning. Here we describe a conditional and dominant mis-sense mutation in the C. elegans alpha-tubulin gene tba-1 that disrupts pronuclear migration and positioning of the first mitotic spindle, and results in a highly penetrant embryonic lethality, at the restrictive temperature of 26 degrees C. Our analysis of the dominant tba-1 (or346ts) allele suggests that TBA-1 assembles into microtubules in early embryonic cells. However, we also show that reduction of tba-1 function using RNA interference results in defects much less severe than those caused by the dominant or346ts mutation, due to partial redundancy of TBA-1 and another alpha-tubulin called TBA-2. Reducing the function of both TBA-1 and TBA-2 results in severe defects in microtubule-dependent processes. We conclude that microtubules in the early C. elegans embryo are composed of both TBA-1 and TBA-2, and that the dominant tba-1(or346ts) mutation disrupts MT assembly or stability. Cell Motil.     

TGF beta-related pathways. Roles in Caenorhabditis elegans development

Genetic and molecular analysis in Caenorhabditis elegans has produced new insights into how TGF beta-related pathways transduce signals and the developmental processes in which they function. These pathways are essential regulators of dauer formation, body-size determination, male copulatory structures and axonal guidance. Here, we review the insights that have come from standard molecular genetic experiments and discuss how the recently completed genome sequence has contributed to our understanding of these pathways.