The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during post-embryonic 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 non-overlapping 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 homozygous 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 non-overlapping 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.