Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans
Program in Molecular Medicine
Adaptor Proteins, Signal Transducing; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Carrier Proteins; Cell Lineage; Disorders of Sex Development; Down-Regulation; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Larva; MicroRNAs; Models, Biological; Phenotype; RNA-Induced Silencing Complex; Signal Transduction
Biochemistry | Developmental Biology | Genomics | Molecular Biology | Molecular Genetics
In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period of interrupted development. For cells to progress to L3 cell fate, the transcription factor Hunchback-like-1 (HBL-1) must be downregulated. Here, we describe a quiescence-induced shift in the repertoire of microRNAs that regulate HBL-1. During continuous development, HBL-1 downregulation (and consequent cell fate progression) relies chiefly on three let-7 family microRNAs, whereas after quiescence, HBL-1 is downregulated primarily by the lin-4 microRNA in combination with an altered set of let-7 family microRNAs. We propose that this shift in microRNA regulation of HBL-1 expression involves an enhancement of the activity of lin-4 and let-7 microRNAs by miRISC modulatory proteins, including NHL-2 and LIN-46. These results illustrate how the employment of alternative genetic regulatory pathways can provide for the robust progression of progenitor cell fates in the face of temporary developmental quiescence.
DOI of Published Version
Development. 2012 Jun;139(12):2177-86. doi: 10.1242/dev.075986. Link to article on publisher's site
Development (Cambridge, England)
Karp, Xantha and Ambros, Victor R., "Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans" (2012). Program in Molecular Medicine Publications and Presentations. 26.