Kim D, Grun D, van Oudenaarden A.. Dampening of expression oscillations by synchronous regulation of a microRNA and its target. Nat Genet 45: 1337-1344

1] Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3].
Nature Genetics (Impact Factor: 29.35). 09/2013; 45(11). DOI: 10.1038/ng.2763
Source: PubMed


The complexity of multicellular organisms requires precise spatiotemporal regulation of gene expression during development. We find that in the nematode Caenorhabditis elegans approximately 2,000 transcripts undergo expression oscillations synchronized with larval transitions while thousands of genes are expressed in temporal gradients, similar to known timing regulators. By counting transcripts in individual worms, we show that pulsatile expression of the microRNA (miRNA) lin-4 maintains the temporal gradient of its target lin-14 by dampening its expression oscillations. Our results demonstrate that this insulation is optimal when pulsatile expression of the miRNA and its target is synchronous. We propose that such a miRNA-mediated incoherent feed-forward loop is a potent filter that prevents the propagation of potentially deleterious fluctuations in gene expression during the development of an organism.

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    • "Degree of developmental stability: Mechanisms such as microguarding are expected to be important and efficient ways in which to carefully fine-tune developmental processes, ensuring the correct balance between developmental signals. Perturbations to these signals will disrupt normal development resulting in potentially significant fitness costs, selecting for any mechanisms that lower gene expression variation (Kim et al., 2013). "
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    • "Developmental timing is usually studied by means of direct observation of the animals at short time intervals using a dissecting microscope. Lethargus, cessation of pharyngeal pumping , ecdysis (Monsalve et al. 2011), and expression of GFP driven by promoters of genes that oscillate with the molts (Kim et al. 2013) have been used as hallmarks of the "
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    ABSTRACT: Caenorhabditis elegans postembryonic development consists of four discrete larval stages separated by molts. Typically, the speed of progression through these larval stages is investigated by visual inspection of the molting process. Here, we describe an automated method to monitor the timing of these discrete phases of C. elegans maturation, from the first larval stage through adulthood, using bioluminescence. The method was validated with a lin-42 mutant strain that shows delayed development relative to wild-type animals and with a daf-2 mutant that shows an extended second larval stage. This new method is inherently high-throughput and will finally allow dissecting the molecular machinery governing the speed of the developmental clock, so far hampered by the lack of a method suitable for genetic screens. Copyright © 2015, The Genetics Society of America.
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    • "As developmental effects were very strong and affected many genes2334, we selected those genes that did not have a developmental effect (P < 0.05) or an effect which was opposite of what one would expect in a relatively slower developed bar-1(ga80) mutant (Supplemental figure C). We also selected on effect size (>0.5 or <−0.5) which resulted in 710 down- and 425 up-regulated genes compared to N2 (FDR = 0.05; Supplement Table 1). "
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