Key Points
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The heterochronic genes of Caenorhabditis elegans control the timing and sequence of several post-embryonic developmental events, including the terminal differentiation of the hypodermis.
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Mutations in heterochronic genes cause hypodermal-cell terminal differentiation to occur too early (precocious phenotype) or too late (retarded phenotype) relative to other unaffected events.
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The 22-nucleotide lin-4 RNA molecule downregulates lin-14 and lin-28 expression at a step subsequent to translation initiation by interacting with antisense complementary sites in the 3′ untranslated regions of their mRNAs.
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Temporal downregulation of LIN-14 and LIN-28 guides development from the first to the third larval stage.
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The let-7 RNA molecule begins to accumulate in the late third larval stage and downregulates lin-41, and possibly other genes, freeing lin-29 to trigger the switch to the terminally differentiated adult stage.
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let-7 is evolutionarily conserved from worms to humans and is developmentally regulated in some organisms, including flies, indicating a temporal regulatory function might also be conserved.
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The production of the small lin-4 and let-7 RNAs uses components required to generate the small double-stranded RNAs involved in the mechanism of RNA interference.
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Hormonal inputs are a common theme in the control of developmental time in diverse animals.
Abstract
The molecular mechanisms that time development are now being deciphered in various organisms, particularly in Caenorhabditis elegans. Key recent findings indicate that certain C. elegans timekeeping genes are conserved across phyla, and their developmental expression patterns indicate that a timing function might also be conserved. Small regulatory RNAs have crucial roles in the timing mechanism, and the cellular machinery required for production of these RNAs intersects with that used to process double-stranded RNAs during RNA interference.
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Acknowledgements
I thank J. Simon, J. Shaw, M. Montgomery, H. Gardner and D. Zarkower for discussions and critical reading of the manuscript and C. Mello and A. Fire for sharing results before publication. My apologies to those whose work could not be cited owing to space constraints. The Rougvie laboratory is supported by the National Institutes of Health.
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Glossary
- BILATERIAN
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An animal that has bilateral symmetry — a form of symmetry in which the body axis can be divided by a sagittal plane into two mirror-image parts.
- DIPLOBLAST
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An animal with only two germ layers (ectoderm and endoderm), including the Cnidaria, Ctenophora and, according to some authors, Placozoa and Porifera.
- HETEROCHRONIC MUTATION
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A heterochronic mutation — from the Greek heteros, meaning other or different, and chronos, meaning time — alters the relative timing of developmental events as an organism grows.
- BLAST CELL
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An undifferentiated precursor cell.
- DAUER LARVA
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Juvenile nematode in which development is arrested during unsuiTable conditions and resumes when conditions improve.
- ADHERENS JUNCTIONS
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Cell–cell adhesive junctions that are linked to cytoskeletal filaments of the micro- filament type.
- EPISTATIC
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When one gene masks the expression of another. If mutant a gives phenotype A and mutant b gives phenotype B, and if the double mutant ab gives phenotype A and not B, then gene a is epistatic to gene b.
- PENETRANCE
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The proportion of genotypically mutant organisms that show the mutant phenotype. If all genotypically mutant individuals show the mutant phenotype, then the genotype is said to be completely penetrant.
- ECDYSONE
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Class of steroid hormones found in insects, crustaceans and some plants. In insects, ecdysone stimulates moulting and metamorphosis.
- PAEDOGENETIC
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A type of animal that shows precocious sexual mating in larval stage.
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Rougvie, A. Control of developmental timing in animals. Nat Rev Genet 2, 690–701 (2001). https://doi.org/10.1038/35088566
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DOI: https://doi.org/10.1038/35088566
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