Between Dec 19, 2024 and Jan 2, 2025, datasets can be submitted to DRUM but will not be processed until after the break. Staff will not be available to answer email during this period, and will not be able to provide DOIs until after Jan 2. If you are in need of a DOI during this period, consider Dryad or OpenICPSR. Submission responses to the UDC may also be delayed during this time.

Browsing by Subject "lin-42"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Analysis of lin-42/period through characterization of a null allele reveals the implications of all three isoforms
    (2016-12) Edelman, Theresa
    The timing of post-embryonic development is regulated by the heterochronic gene pathway in C. elegans. An important member of this pathway is lin-42, the worm homolog of the circadian clock gene period. Existing lin-42 alleles have implicated this gene in developmental timing, molting, and the decision to enter the alternative dauer state. lin-42 is a complex locus, encoding overlapping and non-overlapping isoforms, and as a result hypomorphic alleles leave at least one isoform intact. A null allele is needed to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem, and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein coding region. lin-42 null mutants are homozygous viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. Additional evidence is also provided for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. lin-42 functions in the heterochronic pathway to regulate transcription of primary miRNAs, including the let-7 miRNA family. One member of the let-7 family is mir-48. To better understand how mir-48 fits in the pathway a mir-48 gain-of-function suppressor screen was performed. This screen yielded multiple candidates that could function with mir-48 in the heterochronic gene pathway, as miR-48 target genes, or as regulators of miRNA biogenesis and function. Analysis of these mutants should provide insights into control of developmental time.
  • Thumbnail Image
    Item
    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.