The Developmental Timing Regulator<i>hbl-1</i>Modulates the Dauer Formation Decision in<i>Caenorhabditis elegans</i>

Karp, Xantha; Ambros, Victor R.

doi:10.1534/genetics.110.123992

Cited by 11 publications

(4 citation statements)

References 52 publications

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“…Such networks have been shown to be important for robustness [61] . Also, DAF-12 could secure robustness by positive regulation of dauer loci, such as daf-3 , daf-16 or hbl-1 and by repression of genes that inhibit dauer formation, such as lin-42 [54] , [62] . In addition, the system can buffer perturbations because gene products, such as miRNAs or DIN-1, modulated by DAF-12 can also regulate DAF-12 activity ( Figure 9 ) [19] .…”

Section: Discussionmentioning

confidence: 99%

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

et al. 2011

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The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions.

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Section: Discussionmentioning

confidence: 99%

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

et al. 2011

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“…The key properties of miRNAmediated gene silencing, such as one miRNA targeting multiple mRNAs and one target gene being regulated by multiple miRNAs, suggest that (i) miRNAs are excellent candidate regulators for coordinating multiple aspects of molecular and cellular activities for specific physiological functions and (ii) miRNAs likely function in a synergistic or additive manner to regulate sets of genes under specific physiological conditions that are not limited to those related to development (9). Consistent with these ideas, several recent lines of evidence suggest that miRNA let-7 and the heterochronic genes lin-42 and hbl-1 are required to regulate the starvation-induced dauer diapause (10)(11)(12) and that a number of miRNAs including lin-4 and mir-71 are involved in regulating life span (13,14). Furthermore, a recent study suggests that the expression of certain miRNAs is differentially regulated by starvation-induced dauer diapause (15).…”

mentioning

confidence: 89%

microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause

Zhang

Zabinsky

Teng

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

104

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Environmental stresses and nutrition availability critically affect animal development. Numerous animal species across multiple phyla enter developmental arrest for long-term survival in unfavorable environments and resume development upon stress removal. Here we show that compromising overall microRNA (miRNA) functions or mutating certain individual miRNAs impairs the longterm survival of nematodes during starvation-induced L1 diapause. We provide evidence that miRNA miR-71 is not required for the animals' entry into L1 diapause, but plays a critical role in long-term survival by repressing the expression of insulin receptor/PI3K pathway genes and genes acting downstream or in parallel to the pathway. Furthermore, miR-71 plays a prominent role in developmental recovery from L1 diapause partly through repressing the expression of certain heterochronic genes. The presented results indicate that interactions between multiple miRNAs and likely a large number of their mRNA targets in multiple pathways regulate the response to starvation-induced L1 diapause.F ood deprivation is a life-threatening challenge that animals frequently face as individuals and as species. Different organisms have developed versatile growth arrest strategies to overcome starvation-induced metabolic and developmental problems. The coordinated entrance into developmental arrest, long-term survival, and the reinitiation of development upon food availability are important biological processes to investigate.The nematode Caenorhabditis elegans responds to starvation by entering developmental arrest at multiple stages of its life cycle (1). When late, first larval stage (L1) worms sense unfavorable conditions, they enter an alternative and long-lived larval stage called dauer larvae (or dauer diapause). However, when newly hatched L1 worms encounter an environment with no food, developmental programs arrest and the worm enters L1 diapause. Unlike dauer diapause, L1 diapause is not accompanied by life cycle changes and has not been shown to require certain signaling pathways that control the formation of dauer diapause [such as TGF-β signaling (daf-1, daf-7) and nuclear hormone receptor (daf-12)] (2, 3). Furthermore, worms that are long-lived due to dietary restriction or decreased mitochondrial respiratory rates are short-lived during L1 diapause, suggesting that the mechanisms controlling L1 starvation survival are different at least in some aspects from those controlling aging (3).Previous studies showed that the release of postdocking calciumregulated dense-core vesicles, the insulin receptor (InsR) pathway, the AMPK pathway, and protein chaperones are required for the long-term survival of starved L1 worms (2-4). The roles of InsRs have also been implicated in arresting the cell cycle in germ cells and a portion of somatic cells during L1 diapause (2, 4). Upon entering L1 diapause, RNA polymerase II quickly accumulates and pauses at promoter regions, and this accumulation was speculated to stop transcription and facilitate the immediate reinit...

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“…Interestingly, a role of neuronal miRNAs in preventing aberrant dauer formation has been shown, proposing miRNA-mediated gene silencing as a mechanism that reinforces the robustness of these pathways [18]. In addition, several regulators of developmental timing, including lin-4 and the let-7 -family miRNAs, along with their targets LIN-14, LIN-28, HBL-1 and DAF-12, can modulate dauer formation under adverse conditions [16,17,49,72], while also contributing to the robust developmental progression during post-dauer stages [73]. …”

Section: Discussionmentioning

confidence: 99%

Neuronal function of the mRNA decapping complex determines survival ofCaenorhabditis elegansat high temperature through temporal regulation of heterochronic gene expression

et al. 2017

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In response to adverse environmental cues, Caenorhabditis elegans larvae can temporarily arrest development at the second moult and form dauers, a diapause stage that allows for long-term survival. This process is largely regulated by certain evolutionarily conserved signal transduction pathways, but it is also affected by miRNA-mediated post-transcriptional control of gene expression. The 5′–3′ mRNA decay mechanism contributes to miRNA-mediated silencing of target mRNAs in many organisms but how it affects developmental decisions during normal or stress conditions is largely unknown. Here, we show that loss of the mRNA decapping complex activity acting in the 5′–3′ mRNA decay pathway inhibits dauer formation at the stressful high temperature of 27.5°C, and instead promotes early developmental arrest. Our genetic data suggest that this arrest phenotype correlates with dysregulation of heterochronic gene expression and an aberrant stabilization of lin-14 mRNA at early larval stages. Restoration of neuronal dcap-1 activity was sufficient to rescue growth phenotypes of dcap-1 mutants at both high and normal temperatures, implying the involvement of common developmental timing mechanisms. Our work unveils the crucial role of 5′–3′ mRNA degradation in proper regulation of heterochronic gene expression programmes, which proved to be essential for survival under stressful conditions.

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The Developmental Timing Regulatorhbl-1Modulates the Dauer Formation Decision inCaenorhabditis elegans

Cited by 11 publications

References 52 publications

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause

Neuronal function of the mRNA decapping complex determines survival ofCaenorhabditis elegansat high temperature through temporal regulation of heterochronic gene expression

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