Gene expression

The production of a functional product from a given gene. Gene products can stem from protein coding or non-protein coding sequences. Non-protein coding genes include tRNAs, rRNAs, and microRNAs. The regulation of gene expression, (timing, location, and amount) is the basis for cell specification, differentiation, and morphogenesis during development and allows the animal to respond and adapt to environmental stimuli.

Post-transcriptional RNA binding

Post-transcriptional control of RNA metabolism plays a major role in development and involves proteins that bind to RNA (RBPs). RBP binding has been shown to display tissue-specific activity, which when altered can result in tissue-specific mutant phenotypes. Molecular studies have identified many RBPs that bind regulatory sequences in the 3' untranslated regions of mRNAs. Studies of RBPs in C. elegans seek to provide insights into how RBPs exert coordinate control of their RNA targets and affect development.

Development

Development is the process of temporal and spatial control of gene expression that gives rise to a fully functional adult form of the organism. Studies of development in C. elegans have traced every cell from birth to final differentiated state in the developing nematode. These studies have elucidated cellular, genetic, and molecular mechanisms that control the division, growth, differentiation and morphogenesis of cells giving rise to tissues and organs in the nematode body. While most terminally differentiated cells can be traced by lineage back to a founder cell, there still remains a few cells types in the nematode with stochastic identity, relying on signals from the environment for their final identity.

Metabolism

The chemical reactions, and regulation of these reactions, within an organism that are required for growth, reproduction, maintenance of proper cellular and organ function and structure, and response to the environment. These enzyme-catalyzed processes control all cellular functions including digestion, detoxification, protein synthesis, degradation and modification, and energy production.

RTK/Ras/MAPK signaling pathway

Receptor Tyrosine Kinase (RTK)/Ras GTPase/MAP kinase (MAPK) activated signaling pathways are used repeatedly during metazoan development to control many different biological processes. C. elegans contains two different RTKs (LET-23/EGFR and EGL-15 /FGFR) that are known to stimulate LET-60/Ras and a MAPK cascade consisting of the kinases LIN-45/Raf, MEK-2/MEK and MPK-1/ERK. This Ras/MAPK cascade is required for multiple developmental events, including induction of vulval, uterine, spicule, P12 and excretory duct cell fates, control of sex myoblast migration and axon guidance, and promotion of germline meiosis. Studies in C. elegans have provided much insight into the basic framework of this RTK/Ras/MAPK signaling pathway, its regulation, how it elicits cell-type specific responses, and how it interacts with other signaling pathways such as the Wnt and Notch pathways.

Defecation

In C. elegans the expulsion of intestinal contents occurs every 45-50 seconds. This cycle is characterized by a pattern of muscle contractions under both muscle and neuronal control. The steps of the defecation cycle are a posterior body contraction (pBoc), an anterior body contraction (aBoc), and the final expulsion step (Exp) where the enteric muscles contract, opening the anus and allowing the intestinal contents to be released. Each step is independently controlled as mutations exist that affect one step but do not alter the timing or occurrence of the other. Further, Ca++ oscillations in the intestine, rather than neuronal stimulation, have been shown to control the initiating pBoc step. The contractions of the enteric muscles are controlled by GABA motor neurons AVL and DVB through an excitatory GABA-gated cation channel. The periodicity of the cycle is influenced by the presence of food, is temperature compensated, and can be reset by mechanosensory input.

Egg laying

C. elegans hermaphrodites exhibit a periodicity in the rate and temporal pattern of egg-laying. Egg laying is modulated by diverse environmental cues. Egg laying behavior has served as an important phenotypic assay for the genetic dissection of neuronal signal transduction mechanisms. Studies in C. elegans have elucidated the roles of specific neurons in the egg-laying motor circuit, which release multiple neurotransmitters affecting distinct parameters of egg-laying muscle activity, and the possible mechanisms for sensory control of egg-laying behavior.

Organogenesis

The formation and development of an organ (a structural part of an organism that performs a specialized function) requires the coordination of many intrinsic and extrinsic cues that control cellular processes such as cell division and specificity, cell movement, cell-cell interaction, and cell polarity. C. elegans has proved to be a model organism for studying key organs, e.g., pharynx, intestine, and vulva, in part due to the small number of traceable cells that make up these specialized group of cells.

Response to stress

A stress response is any physical response to factors that upset the normal balance of a biological event. C. elegans nematodes are susceptible to many different environmental stressors that include changes in temperatures, exposure to high osmolarity, and changes in oxygen levels. Internal stressors include DNA damage, accumulation of unfolded proteins, and accumulation of reactive oxygen species. These stressors have been shown to have a strong impact on the lifespan of C. elegans. The regulation of stress responses in the worm are similar to that in other organisms and include modulations of pathways that control caloric intake, mitochondrial respiration, insulin/IGF-1 (IIS), and JNK (c-Jun N-terminal kinase) signaling.

RNA splicing

During pre-messenger RNA (pre-mrRNA) processing, cis-splicing reactions remove non-coding introns and joins coding exons. The majority of splicing is catalyzed by spliceosomes, large RNA-protein complexes composed of small nuclear ribonucleoproteins (snRNPs) that recognize splice donor and acceptor sites within the nascent RNA strand. Alternative mRNAs for a given gene can be created during the splicing reactions through varying the degree of cutting and splicing of introns and exons guided by alternative splice sites. C. elegans also exhibits trans-splicing where sequences from different primary RNA transcripts are used to make the mRNA. In C. elegans, ~70% of transcripts are trans-spliced with either a splice leader sequence SL1 or SL2 joined to the final transcript. Splice leaders are important