Caenorhabditis elegans as a Promising Model Organism in Chronobiology

Abstract

Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms, ranging from bacteria to fungi, plants, and animals. Circadian rhythms are generated by endogenous clocks that can be entrained daily by environmental cycles such as light and temperature. The molecular machinery of circadian clocks includes a transcriptional-translational feedback loop that takes approximately 24 h to complete. Drosophila melanogaster has been a model organism of choice to understand the molecular basis of circadian clocks. However, alternative animal models are also being adopted, each offering their respective experimental advantages. The nematode Caenorhabditis elegans provides an excellent model for genetics and neuro-behavioral studies, which thanks to its ease of use and manipulation, as well as availability of genetic data and mutant strains, is currently used as a novel model for circadian research. Here, we aim to evaluate C. elegans as a model for chronobiological studies, focusing on its strengths and weaknesses while reviewing the available literature. Possible zeitgebers (including light and temperature) are also discussed. Determining the molecular bases and the neural circuitry involved in the central pacemaker of the C. elegans’ clock will contribute to the understanding of its circadian system, becoming a novel model organism for the study of diseases due to alterations of the circadian cycle.

A conserved chronobiological complex timesC. elegansdevelopment

“…mouse PER2 at 1225 amino acids (Jeon et al , 1999). LIN-42 lacks a CRY-binding domain, consistent with a lack of CRY orthologue in C. elegans , and in its tandem PER-ARNT-SIM (PAS) domains, only PAS-B is well conserved, adopts a canonical fold, and mediates dimerization in a mode identical to mammalian PER (Lamberti et al , 2023; Migliori et al , 2023). Finally, two stretches of sequence, previously termed SYQ and LT according to their first amino acids (Tennessen et al , 2006), bear sequence homology to the two PER CK1BD subdomains, CK1BD-A and CK1BD-B, but their function has remained unexplored.…”

“…The extent of functional similarity between these timing systems generally, and LIN-42 and PER function specifically, has remained uncertain, despite the realization that additional orthologues of mammalian clock genes exist and cause heterochronic phenotypes when mutated (Banerjee et al , 2005; Gissendanner et al , 2004; Jeon et al , 1999; Kostrouchova et al , 1998; Hasegawa et al , 2005; Migliori et al , 2023). Conceptually, whereas mutations of circadian clock genes such as PER change the tempo and/or robustness of circadian rhythms, heterochronic mutations are defined by their ability to alter the sequence of developmental events, such that certain events are skipped (Ambros & Horvitz, 1984; Ambros, 1989).…”

Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans

“…Circadian rhythms of physiological and behavioral variables, such as gene expression and locomotor activity, have been observed in the nematode C. elegans 7 ; however, the molecular mechanism of its central pacemaker is currently unknown. With the exception of cry ( cryptochrome ), C. elegans has homologs to other metazoan clock genes such as lin-42 ( period ), kin-20 (CK1ε/δ), aha-1 ( cycle/bmal1 ), nhr-23 ( rorɑ/ɣ ), nhr-85 ( rev-erbɑ/β ), and nhr-25 ( sf-1 ) 8 – 11 .…”

Regulation of the circadian clock inC. elegansby clock gene homologskin-20andlin-42

“…Circadian rhythms of physiological and behavioral variables, such as gene expression and locomotor activity, have been observed in the nematode C. elegans [7]; however, the molecular mechanism of its central pacemaker is currently unknown. With the exception of cry (cryptochrome), C. elegans has homologs to other metazoan clock genes such as lin-42 (period), kin-20 (CK1ε/δ), aha-1 (cycle/bmal1), nhr-23 (rorɑ/ɣ), nhr-85 (rev-erbɑ/β), and nhr-25 (sf-1) [8][9][10][11].…”