Analysis of a lin-42/period null allele implicates all three isoforms in regulation of caenorhabditis elegans molting and developmental timing

Theresa L B Edelman, Katherine A. McCulloch, Angela Barr, Christian Frøkjær-Jensen, Erik M. Jorgensen, Ann E. Rougvie

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele 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 homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence 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. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

Original languageEnglish (US)
Pages (from-to)4077-4086
Number of pages10
JournalG3: Genes, Genomes, Genetics
Volume6
Issue number12
DOIs
StatePublished - Jan 1 2016

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Molting
Caenorhabditis elegans
Protein Isoforms
Alleles
Phenotype
Developmental Genes
Circadian Clocks
Critical Pathways
Open Reading Frames
Genes
Cell Differentiation

Keywords

  • Caenorhabditis elegans
  • Heterochrony
  • Lin-42
  • Molting

Cite this

Analysis of a lin-42/period null allele implicates all three isoforms in regulation of caenorhabditis elegans molting and developmental timing. / Edelman, Theresa L B; McCulloch, Katherine A.; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M.; Rougvie, Ann E.

In: G3: Genes, Genomes, Genetics, Vol. 6, No. 12, 01.01.2016, p. 4077-4086.

Research output: Contribution to journalArticle

Edelman, Theresa L B ; McCulloch, Katherine A. ; Barr, Angela ; Frøkjær-Jensen, Christian ; Jorgensen, Erik M. ; Rougvie, Ann E. / Analysis of a lin-42/period null allele implicates all three isoforms in regulation of caenorhabditis elegans molting and developmental timing. In: G3: Genes, Genomes, Genetics. 2016 ; Vol. 6, No. 12. pp. 4077-4086.
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AB - The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele 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 homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence 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. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

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