Characterization of the function of the <italic>C. elegans</italic> heterochronic gene <italic>lin-42/per</italic> during larval development

Abstract

The heterochronic pathway of <italic>C. elegans</italic> ensures the appropriate timing of post-embryonic development. Mutations in heterochronic genes cause skipping or reiteration of larval programs, resulting in severe developmental defects. Many <italic>C. elegans</italic> heterochronic genes are conserved in both sequence and function; therefore, study of developmental timing in <italic>C. elegans</italic> contributes to understanding of development in other organisms. The heterochronic gene <italic>lin-42</italic> is the <italic>C. elegans</italic> homolog of <italic>period</italic>, a component of the circadian clock of Drosophila and mammals. <italic>lin-42(lf)</italic> results in precocious heterochronic phenotypes, in which later developmental events occur too early. <italic>lin-42</italic> also regulates molting, and <italic>lin-42</italic> mutants have delayed and prolonged larval molts compared to wild-type animals. In my thesis work, I show that <italic>lin-42</italic> confers robustness on developmental and molting pathways against environmental fluctuations, as <italic>lin-42(lf)</italic> heterochronic and molting phenotypes are very sensitive to changes in environment, which is not observed in wild-type animals. Also, I have found that <italic>lin-42</italic> regulates developmental timing by inhibiting expression of let-7-family miRNAs, likely at the level of transcription. Genetic analyses place <italic>lin-42</italic> upstream of this miRNAs, showing that regulation of let-7-family miRNAs is a key function of <italic>lin-42</italic> in the heterochronic pathway.