Similarity of the C. elegans Developmental Timing Protein LIN-42 to Circadian Rhythm Proteins

Abstract

The Caenorhabditis elegans heterochronic genes control the relative timing and sequence of many events during postembryonic development, including the terminal differentiation of the lateral hypodermis, which occurs during the final (fourth) molt. Inactivation of the heterochronic gene lin-42 causes hypodermal terminal differentiation to occur precociously, during the third molt. LIN-42 most closely resembles the Period family of proteins from Drosophila and other organisms, proteins that function in another type of biological timing mechanism: the timing of circadian rhythms. Per mRNA levels oscillate with an approximately 24-hour periodicity. lin-42 mRNA levels also oscillate, but with a faster rhythm; the oscillation occurs relative to the approximately 6-hour molting cycles of postembryonic development.

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

“…Homology to the defining protein-interaction PAS domain of Period proteins, which contains a cytoplasmic localization domain, is found within LIN-42B and LIN-42C. 2 In addition, the SYQ and LT domains (named after their conserved amino acids) found in LIN-42A and LIN-42B are also found within Period proteins. 1 The LT domain is predicted to contain a nuclear localization sequence.…”

“…[2][3][4] Instead of cycling every day, however, LIN-42 oscillates in accordance with the molt throughout the larval stages. [2][3][4] This suggests that LIN-42 plays multiple or continued roles throughout development. LIN-42 is enriched in the nuclei relative to the cytoplasm, but is present in both locations.…”

“…LIN-42 is enriched in the nuclei relative to the cytoplasm, but is present in both locations. 2 The expression pattern of LIN-42 varies in different cell types, and the timing of expression of the different LIN-42 isoforms also varies. 2-4 LIN-42B and C peak during the intermolt, while LIN-42A peaks at the molt.…”

“…2-4 LIN-42B and C peak during the intermolt, while LIN-42A peaks at the molt. [2][3][4] In fact, LIN-42 is necessary for proper molting. 3 Lin-42 (ok2385) worms, which contain a deletion that eliminates all of LIN-42A and LIN-42B exons 6-9, molt asynchronously and spend more time in the lethargic stage prior to ecdysis.…”

“…1 They also have difficulty shedding cuticles and are thus slightly dumpy; this phenotype is exasperated in later stage worms. 2,3 LIN-42 is important for negatively regulating entry into dauer. 4 By acting in opposition to the nuclear receptor and heterochronic gene, daf-12, LIN-42 promotes continuation through the molting cycle under normal or mild stress conditions.…”