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Free keywords:
Activin Receptors, Type I/genetics/metabolism
Animals
Caenorhabditis elegans/cytology/*growth & development/metabolism
Caenorhabditis elegans Proteins/genetics/isolation & purification/*metabolism
Carrier Proteins/genetics/metabolism
Cell Cycle Proteins/genetics/metabolism
Cell Differentiation/*genetics
Conserved Sequence/genetics
Cullin Proteins/genetics/metabolism
Down-Regulation/genetics
Evolution, Molecular
F-Box Proteins/genetics/isolation & purification/*metabolism
Gene Expression Regulation, Developmental/*genetics
Larva/cytology/growth & development/metabolism
Protein-Arginine N-Methyltransferases/genetics/metabolism
RNA Interference
SKP Cullin F-Box Protein Ligases/genetics/metabolism
Abstract:
During metazoan development, cells acquire both positional and temporal identities. The Caenorhabditis elegans heterochronic loci are global regulators of larval temporal fates. Most encode conserved transcriptional and translational factors, which affect stage-appropriate programs in various tissues. Here, we describe dre-1, a heterochronic gene, whose mutant phenotypes include precocious terminal differentiation of epidermal stem cells and altered temporal patterning of gonadal outgrowth. Genetic interactions with other heterochronic loci place dre-1 in the larval-to-adult switch. dre-1 encodes a highly conserved F box protein, suggesting a role in an SCF ubiquitin ligase complex. Accordingly, RNAi knockdown of the C. elegans SKP1-like homolog SKR-1, the cullin CUL-1, and ring finger RBX homologs yielded similar heterochronic phenotypes. DRE-1 and SKR-1 form a complex, as do the human orthologs, hFBXO11 and SKP1, revealing a phyletically ancient interaction. The identification of core components involved in SCF-mediated modification and/or proteolysis suggests an important level of regulation in the heterochronic hierarchy.
