Molting requires precise coordination of developmental and temporal events including not only synchronization amongst tissues but also the coordination of special behaviors, degradation and synthesis of the exoskeleton. Given the global changes of the molting cycle, it is expected that some type of neuroendocrine regulation will be found. In order to discover genes that regulate molting in C. elegans we did a forward genetic screen (in collab. w/ Alison Frand) for genes that are required to cease the molting cycle in adults. We chose to focus on a mutant that, like other retarded heterochronic mutants, molts as an adult, but is unique because it does so out of an adult cuticle. We identified
mg412 as a weak allele of
pqn-47(F59B10.1). Our identification and characterization of additional
pqn-47 alleles have revealed that the gene is required for embryonic development and the earlier larval molts in addition to the cessation of molting in adults. A hint of an earlier function was that pqn-47RNAi causes larval arrest with a defective molt phenotype. We found that a deletion allele from the Mitani collection (thank you)
pqn-47(
tm2707) causes a similar phenotype. Surveying lethals in the region identified candidate loci including
let-25 (Herman RK, 1978) and
emb-23 (Cassada, R et al 1981) in which we found mutations in the
pqn-47 ORF.
emb-23 causes embryonic lethality at NPT, suggesting that maternal contribution of
pqn-47 allows embryonic development, whereas zygotic expression becomes required for the first larval molt. We are trying to understand why
mg412 causes an adult molt.
pqn-47 encodes a large uncharacterized protein of unknown function and an excess of glutamine residues, though it has strong conservation in fly and human. The conserved domain has no annotated function, and orthologues in other species have not yet been implicated in any processes, although the human orthologue C11orf9 is highly expressed in neuronal tissue and is upregulated in metastatic cancers and in EMT cancer models. PQN-47 is expressed in neurons and other tissues in perinuclear dots that maybe ER. These studies have the potential to contribute to our understanding of the regulation of molting in C. elegans and elucidate the function of a new class of proteins involved in cell proliferation and differentiation.