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Genetics,
2013]
It is widely appreciated that larvae of the nematode Caenorhabditis elegans arrest development by forming dauer larvae in response to multiple unfavorable environmental conditions. C. elegans larvae can also reversibly arrest development earlier, during the first larval stage (L1), in response to starvation. "L1 arrest" (also known as "L1 diapause") occurs without morphological modification but is accompanied by increased stress resistance. Caloric restriction and periodic fasting can extend adult lifespan, and developmental models are critical to understanding how the animal is buffered from fluctuations in nutrient availability, impacting lifespan. L1 arrest provides an opportunity to study nutritional control of development. Given its relevance to aging, diabetes, obesity and cancer, interest in L1 arrest is increasing, and signaling pathways and gene regulatory mechanisms controlling arrest and recovery have been characterized. Insulin-like signaling is a critical regulator, and it is modified by and acts through microRNAs. DAF-18/PTEN, AMP-activated kinase and fatty acid biosynthesis are also involved. The nervous system, epidermis, and intestine contribute systemically to regulation of arrest, but cell-autonomous signaling likely contributes to regulation in the germline. A relatively small number of genes affecting starvation survival during L1 arrest are known, and many of them also affect adult lifespan, reflecting a common genetic basis ripe for exploration. mRNA expression is well characterized during arrest, recovery, and normal L1 development, providing a metazoan model for nutritional control of gene expression. In particular, post-recruitment regulation of RNA polymerase II is under nutritional control, potentially contributing to a rapid and coordinated response to feeding. The phenomenology of L1 arrest will be reviewed, as well as regulation of developmental arrest and starvation survival by various signaling pathways and gene regulatory mechanisms.
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Stadler Genetics Symposium,
1977]
C. elegans is a roundworm, a free-living soil nematode. The dauer larva is a non-feeding, non-growing larval stage which is formed under conditions of starvation. It possesses a relatively impermeable cuticle and differs from all other larval stages in behavior and morphology. Dauer larva formation is a "developmental switch" in the life cycle which offers special advantages for genetic study. A partial genetic pathway for dauer larva formation has been established. Genetic characterization of additional mutants should reveal more details of this pathway. One class of mutants already characterized exhibits morphological alterations in sensory neurons, as determined by electron microscopy. Such mutants are useful for the study of nerve morphogenesis.
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Alzheimer Dis Assoc Disord,
2003]
The soil nematode Caenorhabditis elegans is a relatively simple organism for the study of animal development and behavior. The worm is conceived as a single cell and undergoes a complex process of development through four larval stages (L1-L4) before it reaches adulthood and lays eggs. It takes approximately 3 days to develop through the larval stages. After reproduction it gradually ages, loses vigor, and dies, usually within 2 to 3 weeks.
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Curr Biol,
2005]
Despite low global diversity among natural populations of Caenorhabditis elegans, neighboring populations can be as genetically distinct as strains from different continents, probably owing to transient bottlenecks and ongoing dispersal as a dauer larva. Selfing predominates in the wild, but rare outcrossing may also play an important role.
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Trends Biochem Sci,
2002]
The FOXO family of Forkhead transcription factors, FKHR (FOXO1), FKHR-L1 (FOXO3a) and AFX (FOXO4), are regulated by the phosphoinositide-3-kinase-protein-kinase-B (PI3K-PKB/c-Akt) pathway. Direct phosphorylation by PKB results in cytoplasmic retention and inactivation, inhibiting the expression of FOXO-regulated genes, which control the cell cycle, cell death, cell metabolism and oxidative stress. This pathway appears to be well conserved throughout evolution. In the nematode Caenorhabditis elegans, it affects lifespan and controls dauer formation. Recent discoveries about FOXO regulation by PI3K-PKB signalling suggest that the PI3K-PKB-FOXO pathway might participate in similar processes in higher eukaryotes.
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Dev Dyn,
2010]
The L1 family of cell adhesion molecules (L1CAMs) in vertebrates has long been studied for its roles in nervous system development and function. Members of this family have been associated with distinct neurological disorders that include CRASH, autism, 3p syndrome, and schizophrenia. The conservation of L1CAMs in Drosophila and Caenorhabditis elegans allows the opportunity to take advantage of these simple model organisms and their accessible genetic manipulations to dissect L1CAM functions and mechanisms of action. This review summarizes the discoveries of L1CAMs made in C. elegans, showcasing this simple model organism as a powerful system to uncover L1CAM mechanisms and roles in healthy and diseased states.
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Adv Genet,
2021]
Developmental programs are under strict genetic control that favors robustness of the process. In order to guarantee the same outcome in different environmental situations, development is modulated by input pathways, which inform about external conditions. In the nematode Caenorhabditis elegans, the process of postembryonic development involves a series of stereotypic cell divisions, the progression of which is controlled by the nutritional status of the animal. C. elegans can arrest development at different larval stages, leading to cell arrest of the relevant divisions of the stage. This means that studying the nutritional control of development in C. elegans we can learn about the mechanisms controlling cell division in an in vivo model. In this work, we reviewed the current knowledge about the nutrient sensing pathways that control the progression or arrest of development in response to nutrient availability, with a special focus on the arrest at the L1 stage.
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Neurochem Res,
2013]
To perform their diverse biological functions the adhesion activities of the cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) might be regulated by local clustering, proteolytical shedding of their ectodomains or rapid recycling to and from the plasma membrane. Another form of regulation of adhesion might be obtained through flexible ectodomains of IgCAMs which adopt distinct conformations and which in turn modulate their adhesion activity. Here, we discuss variations in the conformation of the extracellular domains of CEACAM1 and CAR that might influence their binding and signaling activities. Furthermore, we concentrate on alternative splicing of single domains and short segments in the extracellular regions of L1 subfamily members that might affect the organization of the N-terminal located Ig-like domains. In particular, we discuss variations of the linker sequence between Ig-like domains 2 and 3 (D2 and D3) that is required for the horseshoe conformation.
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Autophagy,
2007]
Autophagy is a catabolic process in which long-lived proteins and organelles are degraded for recycling in the cytoplasm. In the nematode Caenorhabditis elegans autophagy is associated with formation of the dauer larva, an alternative developmental stage that worms can enter under poor growth conditions. We have shown that C. elegans mutants that experience caloric restriction because they are feeding-defective also exhibit elevated autophagy and decreased levels of fat deposits, as well as smaller cells and, consequently, a smaller body size. Our results suggest novel relationships between caloric restriction, longevity, body size and autophagy.
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IUBMB Life,
2009]
Dauer is a dormancy state that may occur at the end of developmental stage L1 or L2 of Caenorhabditis elegans when the environmental conditions are unfavorable (e.g., lack of food, high temperature, or overcrowding) for further growth. Dauer is a nonaging duration that does not affect the postdauer adult lifespan. Major molecular events would include the sensing of the environmental cues, the transduction of the signals into the cells, and the subsequent integration of the signals that result in the corresponding alteration of the metabolism and morphology of the organism. Genetics approach has been effectively used in identifying many of the so-called daf genes involved in dauer formation using C. elegans as the model. Nevertheless, biochemical studies at the protein and metabolic level has been lacking behind in understanding this important life phenomenon. This review focuses on the biochemical understanding so far achieved on dauer formation and dormancy in general, as well as important issues that need to be addressed in the future.