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Browsing by Subject "let-7"

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    Characterization of the function of the C. elegans heterochronic gene lin-42/per during larval development
    (2013-12) McCulloch, Katherine Ann
    The heterochronic pathway of C. elegans 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 C. elegans heterochronic genes are conserved in both sequence and function; therefore, study of developmental timing in C. elegans contributes to understanding of development in other organisms. The heterochronic gene lin-42 is the C. elegans homolog of period, a component of the circadian clock of Drosophila and mammals. lin-42(lf) results in precocious heterochronic phenotypes, in which later developmental events occur too early. lin-42 also regulates molting, and lin-42 mutants have delayed and prolonged larval molts compared to wild-type animals. In my thesis work, I show that lin-42 confers robustness on developmental and molting pathways against environmental fluctuations, as lin-42(lf) heterochronic and molting phenotypes are very sensitive to changes in environment, which is not observed in wild-type animals. Also, I have found that lin-42 regulates developmental timing by inhibiting expression of let-7-family miRNAs, likely at the level of transcription. Genetic analyses place lin-42 upstream of this miRNAs, showing that regulation of let-7-family miRNAs is a key function of lin-42 in the heterochronic pathway.