Genetic control of programmed cell death in the nematode C. elegans

The wild-type functions of the genes ced-3 and ced-4 are required for the initiation of programmed cell deaths in the nematode Caenorhabditis elegans. The reduction or loss of ced-3 or ced-4 function results in a transformation in the fates of cells that normally die; in ced-3 or ced-4 mutants, such cells instead survive and differentiate, adopting fates that in the wild type and associated with other cells. ced-3 and ced-4 mutants appear grossly normal in morphology and behavior, indicating that programmed cell death is not an essential aspect of nematode development. The genes ced-3 and ced-4 define the first known step of a developmental pathway for programmed cell death, suggesting that these genes may be involved in determining which cells die during C. elegans development.     

Selective silencing of cell communication influences anteroposterior pattern formation in C. elegans

In C. elegans males, laterally located V cells generate a simple pattern of anterior alae (cuticular ridges) and posterior rays (mating sensilla). We have found that this pattern is generated, at least in part, by the selective interruption of cell-cell interactions. In anterior V cells, lineages leading to the production of alae are induced by cell interactions. These cell interactions are inhibited in specific posterior V cells by the activity of the gene pal-1, which allows these cells to generate rays instead of alae. The activities of cell signals and pal-1 appear to influence V cell fates by determining the state of a developmental switch that involves two homeotic genes, lin-22 and mab-5.     

Cell-cell interactions that specify certain cell fates in C. elegans development

Cell-cell interactions are important for several cell fate decisions during C. elegans development. Two genes, lin-12 and glp-1, encode similar predicted transmembrane proteins that are members of a potentially ubiquitous family of proteins that may mediate intercellular communication.     

Genetic instability of C. elegans comes naturally

There have been many attempts to measure the genome-wide mutation rate for spontaneous mutations, using measurements of traits in inbred lines in which mutations have accumulated. However, these are likely to miss many small-effect mutations that are important for evolutionary processes. Recently, the genome-wide spontaneous mutation rate in inbred lines of Caenorhabditis elegans was estimated, using DNA sequencing. The results imply that the mutation rate is surprisingly high, and that insertion-deletion mutations are unexpectedly common. Phenotypic assays of the same lines detected only a small proportion of mutations that were predicted to have evolutionarily significant fitness effects.     

The cell cycle and development: lessons from C. elegans

The invariant developmental cell lineage of Caenorhabditis elegans (and other similar nematodes) provides one of the best examples of how cell division patterns can be precisely coordinated with cell fates. Although the field has made substantial progress towards elucidating the many factors that control the acquisition of individual cell or tissue-specific identities, the interplay between these determinants and core regulators of the cell cycle is just beginning to be understood. This review provides an overview of the known mechanisms that govern somatic cell growth, proliferation, and differentiation in C. elegans. In particular, I will focus on those studies that have uncovered novel genes or mechanisms, and which may enhance our understanding of corresponding processes in other organisms.     

On the control of germ cell development in Caenorhabditis elegans

After hatching, the germ line progenitor cells in C. elegans begin to divide mitotically; later, some of the germ line cells enter meiosis and differentiate into gametes. In the adult, mitotic germ cells, or stem cells, are found at one end (the distal end) and meiotic cells occupy the rest of the elongate gonad. Removal of two somatic gonadal cells, the distal tip cells, by laser microsurgery has a dramatic effect on germ cell development. In either sex, this operation leads to the arrest of mitosis and the initiation of meiosis in germ cells. The function of the distal tip cell in the intact animal appears to be the inhibition of meiosis (or stimulation of mitosis) in nearby germ cells. During development, this permits growth and, in the adult, it maintains the germ line stem cell population. A change in the position of the distal tip cell in the gonad at an early point in development is correlated with a change in the axial polarity of the germ line tissue. This suggests that the localization of the distal tip cell's inhibitory activity at the distal end of the gonad establishes the axial polarity of the germ line tissue in the intact animal.     

Chemosensory regulation of development in C. elegans

The dauer larva is a specialized third-larval stage of Caenorhabditis elegans that is long-lived and resistant to environmental insult. The dauer larva is formed in response to a high external concentration of a constitu-tively secreted pheromone. Response to the dauer-inducing pheromone of C. elegans is a promising genetic model for metazoan chemosensory transduction. More than 20 genes have been identified that are required for normal pheromone response. The functions of these genes include production of the pheromone, exposure of sensory neuron endings to the environment, structural and functional integrity of those sensory endings, and the capacity of sensory neurons to make appropriate output. Genetic evidence suggests that two partially redundant sensory pathways act in concert to control dauer formation. At least two classes of chemosensory neurons, ADF and ASI, are implicated in the pheromone response. On the basis of on these findings, a speculative model for the pheromone response is proposed. In this model, the neurons ADF and ASI are pheromone sensors that repress dauer formation in the absence of pheromone and dere-press dauer formation in response to pheromone. It is currently unclear whether or not the two genetically defined sensory pathways both act in ADF and ASI.     

Genetic regulation of unsaturated fatty acid composition in C. elegans

Delta-9 desaturases, also known as stearoyl-CoA desaturases, are lipogenic enzymes responsible for the generation of vital components of membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, and gene expression studies of strains carrying mutations in nhr-80 and in the three genes encoding delta-9 desaturases, fat-5, fat-6, and fat-7. The delta-9 desaturase single mutants display only subtle changes in fatty acid composition and no other visible phenotypes, yet the fat-5;fat-6;fat-7 triple mutant is lethal, revealing that endogenous production of monounsaturated fatty acids is essential for survival. In the absence of FAT-6 or FAT-7, the expression of the remaining desaturases increases, and this ability to compensate depends on NHR-80. We conclude that, like mammals, C. elegans requires adequate synthesis of unsaturated fatty acids and maintains complex regulation of the delta-9 desaturases to achieve optimal fatty acid composition.     

Codon adaptation-based control of protein expression in C. elegans

We present a method to control protein levels under native genetic regulation in Caenorhabditis elegans by using synthetic genes with adapted codons. We found that the force acting on the spindle in C. elegans embryos was related to the amount of the G-protein regulator GPR-1/2. Codon-adapted versions of any C. elegans gene can be designed using our web tool, C. elegans codon adapter.     

Investigating C. elegans development through mosaic analysis

The analysis of genetically mosaic worms, in which some cells carry a wild-type gene and others are homozygous mutant, can reveal where in the animal a gene acts to prevent the appearance of a mutant phenotype. In this primer article, we describe how Caenorhabditis elegans genetic mosaics are generated, identified and analyzed, and we discuss examples in which the analysis of mosaic worms has provided important information about the development of this organism.     

Chromosome-wide control of meiotic crossing over in C. elegans

A central event in sexual reproduction is the reduction in chromosome number that occurs at the meiosis I division. Most eukaryotes rely on crossing over between homologs, and the resulting chiasmata, to direct meiosis I chromosome segregation, yet make very few crossovers per chromosome pair. This indicates that meiotic recombination must be tightly regulated to ensure that each chromosome pair enjoys the crossover necessary to ensure correct segregation. Here, we investigate control of meiotic crossing over in Caenorhabditis elegans, which averages only one crossover per chromosome pair per meiosis, by constructing genetic maps of end-to-end fusions of whole chromosomes. Fusion of chromosomes removes the requirement for a crossover in each component chromosome segment and thereby reveals a propensity to restrict the number of crossovers such that pairs of fusion chromosomes composed of two or even three whole chromosomes enjoy but a single crossover in the majority of meioses. This regulation can operate over physical distances encompassing half the genome. The meiotic behavior of heterozygous fusion chromosomes further suggests that continuous meiotic chromosome axes, or structures that depend on properly assembled axes, may be important for crossover regulation.     

Genetic and epigenetic control of transfer cell development in plants

The inter-cellular translocation of nutrients in plant is mediated by highly specialized transfer cells(TCs).TCs share similar functional and structural features across a wide range of plant species, including location at plant exchange surfaces, rich in secondary wall ingrowths, facilitation of nutrient flow, and passage of select molecules. The fate of endosperm TCs is determined in the TC fate acquisition stage(TCF), before the structure features are formed in the TC differentiation stage(TCD). At present, the molecular basis of TC development in plants remains largely unknown. In this review, we summarize the important roles of the signaling molecules in different development phases, such as sugars in TCF and phytohormones in TCD, and discuss the genetic and epigenetic factors, including TC-specific genes and endogenous plant peptides, and their crosstalk with these signaling molecules as a complex regulatory network in regulation of TC development in plants.     

Sensory activity affects sensory axon development in C. elegans

The simple nervous system of the nematode C. elegans consists of 302 neurons with highly reproducible morphologies, suggesting a hard-wired program of axon guidance. Surprisingly, we show here that sensory activity shapes sensory axon morphology in C. elegans. A class of mutants with deformed sensory cilia at their dendrite endings have extra axon branches, suggesting that sensory deprivation disrupts axon outgrowth. Mutations that alter calcium channels or membrane potential cause similar defects. Cell-specific perturbations of sensory activity can cause cell-autonomous changes in axon morphology. Although the sensory axons initially reach their targets in the embryo, the mutations that alter sensory activity cause extra axon growth late in development. Thus, perturbations of activity affect the maintenance of sensory axon morphology after an initial pattern of innervation is established. This system provides a genetically tractable model for identifying molecular mechanisms linking neuronal activity to nervous system structure.     

Mechanisms of cell positioning during C. elegans gastrulation

Cell rearrangements are crucial during development. In this study, we use C. elegans gastrulation as a simple model to investigate the mechanisms of cell positioning. During C. elegans gastrulation, two endodermal precursor cells move from the ventral surface to the center of the embryo, leaving a gap between these ingressing cells and the eggshell. Six neighboring cells converge under the endodermal precursors, filling this gap. Using an in vitro system, we observed that these movements occurred consistently in the absence of the eggshell and the vitelline envelope. We found that movement of the neighbors towards each other is not dependent on chemotactic signaling between these cells. We further found that C. elegans gastrulation requires intact microfilaments, but not microtubules. The primary mechanism of microfilament-based motility does not appear to be through protrusive structures, such as lamellipodia or filopodia. Instead, our results suggest an alternative mechanism. We found that myosin activity is required for gastrulation, that the apical sides of the ingressing cells contract, and that the ingressing cells determine the direction of movement of their neighboring cells. Based on these results, we propose that ingression is driven by an actomyosin-based contraction of the apical side of the ingressing cells, which pulls neighboring cells underneath. We conclude that apical constriction can function to position blastomeres in early embryos, even before anchoring junctions form between cells.