miRNAs give worms the time of their lives: Small RNAs and temporal control in <i>Caenorhabditis elegans</i>

Resnick, Tamar D.; McCulloch, Katherine A; Rougvie, Ann E.

doi:10.1002/dvdy.22260

Cited by 49 publications

(54 citation statements)

References 111 publications

(221 reference statements)

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“…Instead, some downstream genes repress genes upstream in the pathway, while other genes have multiple targets. 7,8 Heterochronic defects can be analyzed in any cell lineage that displays specific, methodical phenotypes throughout development. For example, most lateral hypodermal cells, otherwise known as seam cells, divide before each molt.…”

Section: Lin-42 and The Heterochronic Pathwaymentioning

confidence: 99%

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Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Wynsberghe¹,

Pasquinelli²

2014

Worm

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Expression from both a let-7 miRNA and a lin-4 miRNA transcriptional reporter were enhanced in the absence of lin-42. Additionally, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) of late larval stage worms showed that LIN-42 bound the let-7 promoter, suggesting that LIN-42 affects mature miRNA levels by inhibiting their transcription. In addition to miRNAs, LIN-42 also predominantly bound to the promoters of many diverse protein-coding genes. These findings support the action of LIN-42 at multiple points within the heterochronic and other regulatory pathways to impact a multitude of functions including developmental timing.

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Section: Lin-42 and The Heterochronic Pathwaymentioning

confidence: 99%

“…Consequently depending on the larval stage affected, heterochronic mutants may vary in the number of seam cells and the timing of seam cell fusion and alae production. 8 Central to the heterochronic pathway are the first discovered microRNAs (miRNAs), lin-4 and let-7. miRNAs act Figure 1.…”

Section: Lin-42 and The Heterochronic Pathwaymentioning

confidence: 99%

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Wynsberghe¹,

Pasquinelli²

2014

Worm

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“…After their final division in the L4, the 16 seam cells exit the cell cycle and differentiate, fusing to form a single cell running the length of the animal that secretes the specialized cuticular structures called alae (Joshi et al, 2010). The proper temporal regulation of seam cell behavior, including the timing of the L2 proliferative division and their terminal differentiation, is controlled by the heterochronic pathway of temporal developmental regulators (Nimmo and Slack, 2009;Resnick et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

C. elegansGATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells

2013

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SUMMARYThe C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development. KEY WORDS: C. elegans, Wnt signaling, Asymmetric cell divisionC. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells

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“…This observation led several researchers to speculate that lin-28 is regulated by let-7 miRNAs, but this hypothesis has never been demonstrated experimentally (Reinhart et al 2000;Resnick et al 2010;Ambros 2011). The only evidence that lin-28 acts downstream of let-7 family miRNAs comes from an investigation of three redundant let-7 family members, miR-48, miR-84, and miR-241, referred to collectively as the "3let-7s" (Abbott et al 2005).…”

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confidence: 99%

Stage-Specific Timing of the microRNA Regulation oflin-28by the Heterochronic Genelin-14inCaenorhabditis elegans

et al. 2017

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In normal development, the order and synchrony of diverse developmental events must be explicitly controlled. In the nematode Caenorhabditis elegans, the timing of larval events is regulated by hierarchy of proteins and microRNAs (miRNAs) known as the heterochronic pathway. These regulators are organized in feedforward and feedback interactions to form a robust mechanism for specifying the timing and execution of cell fates at successive stages. One member of this pathway is the RNA binding protein LIN-28, which promotes pluripotency and cell fate decisions in successive stages. Two genetic circuits control LIN-28 abundance: it is negatively regulated by the miRNA lin-4, and positively regulated by the transcription factor LIN-14 through a mechanism that was previously unknown. In this report, we used animals that lack lin-4 to elucidate LIN-14's activity in this circuit. We demonstrate that three let-7 family miRNAs-miR-48, miR-84, and miR-241-inhibit lin-28 expression. Furthermore, we show genetically that these miRNAs act between lin-14 and lin-28, and that they comprise the pathway by which lin-14 positively regulates lin-28. We also show that the lin-4 family member mir-237, also regulates early cell fates. Finally, we show that the expression of these miRNAs is directly inhibited by lin-14 activity, making them the first known targets of lin-14 that act in the heterochronic pathway.

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miRNAs give worms the time of their lives: Small RNAs and temporal control in Caenorhabditis elegans

Cited by 49 publications

References 111 publications

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

Period homolog LIN-42 regulates miRNA transcription to impact developmental timing

C. elegansGATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells

Stage-Specific Timing of the microRNA Regulation oflin-28by the Heterochronic Genelin-14inCaenorhabditis elegans

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