UMMS Affiliation
Program in Molecular Medicine
Publication Date
2009-11-03
Document Type
Article
Subjects
Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; *Environment; *Feedback, Physiological; Gene Expression Regulation, Developmental; Ligands; MicroRNAs; Models, Biological; Mutation; Receptors, Cytoplasmic and Nuclear; Time Factors
Disciplines
Developmental Biology | Genetics | Molecular Biology | Molecular Genetics
Abstract
Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis elegans to develop rapidly through four larval stages (L1-L4) to the reproductive adult. In unfavorable conditions, L2 larvae can enter the developmentally quiescent, stress-resistant dauer larva stage, enabling them to survive for prolonged periods before completing development. A specific progression of cell division and differentiation events occurs with fidelity during the larval stages, regardless of whether an animal undergoes continuous or dauer-interrupted development. The temporal patterning of developmental events is controlled by the heterochronic genes, whose products include microRNAs (miRNAs) and regulatory proteins. One of these proteins, the DAF-12 nuclear hormone receptor, modulates the transcription of certain let-7-family miRNAs, and also mediates the choice between the continuous vs. dauer-interrupted life history. Here, we report a complex feedback loop between DAF-12 and the let-7-family miRNAs involving both the repression of DAF-12 by let-7-family miRNAs and the ligand-modulated transcriptional activation and repression of the let-7-Fam miRNAs by DAF-12. We propose that this feedback loop functions to ensure robustness of cell fate decisions and to coordinate cell fate with developmental arrest.
Keywords
gene regulation, microRNA, nuclear hormone receptor
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.
DOI of Published Version
10.1073/pnas.0908131106
Source
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18668-73. doi: 10.1073/pnas.0908131106. Epub 2009 Oct 14. Link to article on publisher's site
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
Related Resources
PubMed ID
19828440
Repository Citation
Hammell, Christopher M.; Karp, Xantha; and Ambros, Victor R., "A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans" (2009). Program in Molecular Medicine Publications and Presentations. 32.
https://escholarship.umassmed.edu/pmm_pp/32
Included in
Developmental Biology Commons, Genetics Commons, Molecular Biology Commons, Molecular Genetics Commons