Response to thermal stress

Thermal stress can occur whenever the temperature exceeds the optimal for the animal. In C. elegans at least one response to heat stress involves activation of heat shock proteins that provide protection from cellular damage induced by the elevated temperature. If heat stress occurs during the L1 stage of development, the nematode can enter dauer stage rather than continue to develop to reproductive maturity.

Anaphase

In C. elegans, anaphase is comprised of two separable components, anaphase A, where the chromosomes separate from each other before any chromosome to pole movement, and anaphase B, where the spindle poles move away from each other, with the concomitant movement of the chromosomes to the poles. During anaphase B, the movement of the spindles, which carry the chromosomes, occurs through a combination of pulling and pushing forces. Cortical forces attached at the centrosomes pull the microtubule asters away from one another, while central spindle forces from overlapping microtubule arrays that had formed between separating chromosomes, push the chromosomes away from one another. The holocentric nature of C. elegans chromosomes entails special consideration to ensure the forces at all of the microtubule attachment sites of the chromosome are coordinated so that shearing of the chromosome during segregation does not occur.

Hormesis

The process whereby a low exposure to a toxin or stressor produces a generally positive response in the animal that is the opposite effect produced in response to a higher exposure. This can be observed in cases where C. elegans is exposed to short doses of temperature stress during development. Under such limited exposures, animals exhibit a longer life span than animals reared at room temperature. However, extended exposure to thermal stress results in severely shortened lifespans.

Intestine development

The C. elegans intestine is attached to the posterior pharynx and extends the length of the worm, ending at the rectum. This major organ of the worm consists of 20 large, polyploid epithelial cells arranged in pairs, forming a tube. The intestine is responsible for food digestion, nutrient absorption, and synthesizing and storing macromomlecules such as fat droplets and birefringent gut granules. The intestine also plays major roles in the rhythmic behavior of the defecation cycle as well as stress responses and lifespan.

DNA damage response

DNA damage can occur during normal recombination events or result from various insults, such as exposure to chemical mutagens or exposure to radiation. Metazoans have evolved mechanisms to detect, assess, and deal with any damage at specific checkpoints during the cell cycle. Studies in yeasts and mammals have identified several genes that are required for proper activation of cell cycle check-points following various types of DNA damage. However, in these metazoans, DNA damage can induce apoptosis as well. The inability to efficiently repair DNA damage or remove cells with severely damaged genomes has been linked to several human cancers.

Trans-splicing

Trans-splicing is an RNA processing event that fuses together sections of two different pre-mRNA sequences. In C. elegans, ~70% of mRNAs are trans-spliced to one of two 22 nucleotide spliced leaders, SL1 or SL2, with more than half of all transcripts undergoing SL1 splicing. During SL1 splicing, the 5' ends of pre-mRNAs are removed and replaced with SL1 sequence in a process very closely related to cis-splicing (intron/exon processing). SL1 sequence is ~100nt and is donated by small nuclear ribonucleoprotein particles (snRNPs). The remaining genes are trans-spliced by SL2. These genes are all downstream genes in closely spaced gene clusters similar to bacterial operons. They are transcribed from a promoter at the 5' end of the cluster of between 2 and 8 genes. This transcription makes a polycistronic pre-mRNA that is co-transcriptionally processed by cleavage and polyadenylation at the 3' end of each gene, and this event is closely coupled to the SL2 trans-splicing event that occurs only ~100 nt further downstream. Recent studies on the mechanism of SL2 trans-splicing have revealed that one of the 3' end formation proteins, CstF, interacts with the only protein known to be specific to the SL2 snRNP.

Response to toxicity

Exposure to a toxic substance can activate any number of processes that result in a change in state or activity of the organism. As a soil dwelling organism, C. elegans has evolved defenses against damaging substances in the soil environment and as such has proved to be an ideal organism for studying biological responses to toxins. These responses can occur at an organism level, such as invoking an avoidance behavior, or on a cellular level, such as activation of a cellular stress response. Cellular defenses have been shown to be invoked in response to reactive oxygen species, heavy metals, and toxin-induced unfolded proteins.

Neurotransmission

Neurons communicate across synaptic junctions with target cells, such as neurons, muscles, or specialized secretory cells through chemical messengers that are released from the neuron and bind to and activate receptors on the target cell. Pre-synaptic release of neurotransmitters can be evoked, such as through mechanical or chemical stimulation, as well as can occur spontaneously at a low rate. Depending on the neurotransmitter released and or the receptors of the post-synaptic cell, the activation of receptors can trigger excitatory or inhibitory actions in the target cell. These neuronal communications can also result in short term post-synapatic cellular changes to the membrane potential or can cause the activation of signaling cascades, resulting in longer term changes in the cell.

Embryogenesis

The process by which an embryo forms and develops, marking a time of rapid cell proliferation, specification, and differentiation. Embryogenesis in C. elegans takes about fourteen hours at 22 degrees C, starting with fertilization of the oocyte with self-sperm from the hermaphrodite or sperm from a male. During the first two hours, the zygote forms and early cleavages establish the embryonic axes. Somatic and germ-line founder cell fates are also determined. During the next five hours, most cell proliferation completes, the embryo undergoes gastrulation, and cell differentiation and organogenesis begins. Cell differentiation, organogenesis and morphogenesis are completed during the final stage of embryogenesis. The nervous system becomes active and muscles are stimulated during this last stage, resulting in the embryo twitching within its egg shell and eventually hatching as an L1 larva.

Aging

Aging in C. elegans involves measurable declines in morphology, reproduction, and behavior. Understanding the cellular and molecular processes leading to senescence in this nematode began in the early 1980s with the targeted identification of mutants with extended life spans (an AGE phenotype). These studies identified at least two key regulators of life span, DAF-2, an insulin/IGF receptor ortholog, and DAF-16, a Forkhead-related transcription factor. Since then many more genes and pathways involved in senescence have been identified. Almost all of these genes play important roles in cellular and organismal-level processes other than aging, such as dauer formation, stress response, feeding, and chemosensation. A common marker for aging in C. elegans is the accumulation of lysosomal deposits of lipofuscin, resulting in an increase in intestinal autofluorescence over time.