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6 publications mentioning dre-mir-218b

Open access articles that are associated with the species Danio rerio and mention the gene name mir-218b. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 233
Although we do not know whether the slit2 is expressed in proepicardial cells, it is tempting to speculate that the up regulation of the Tbx5- miR-218 circuit might also impact the proepicardial cell migration by targeting robo1 or other cell migration regulators such as Semaphorins, some members of this large class of molecules being predicted targets of miR-218 (not shown). [score:9]
Tbx5 over -expression tripled slit2 expression, almost doubled miR-218 expression and had no effect on slit3 expression (Fig. 1C). [score:9]
To verify whether miR-218 over -expression can affect cardiac valve development, we analyzed the expression of the tie-2 gene, a member of the Tie family of tyrosine kinase receptors, which is expressed mainly in endothelial cells [31] and is up regulated during atrio-ventricular canal differentiation [32], [33]. [score:9]
Moreover, the transfection of a siRNA mix against Slit2 cut the level of Slit2 by half without affecting miR-218 expression, supporting the idea that miR-218 expression depends on the regulation of Slit2 transcription rather than on its translation. [score:8]
Interestingly, down-regulation of miR-218 is able to rescue most of the defects generated by Tbx5 over -expression, demonstrating the pivotal role of miR-218 in mediating the effects of Tbx5 dosage on heart development. [score:7]
To show that the slit/ miR-218 increase was at least partially dependent on Tbx5, tbx5 was up- or down-regulated by transfecting P19CL6 cells with a tbx5-carrying expression vector (CMV-Tbx5), or with a siRNA mix directed against tbx5, respectively. [score:7]
slit3 expression was also analyzed since its host miRNA, miR-218-2, cannot be separately quantified because it is identical to miR-218-1. In agreement with the literature [19], we observed tight co -expression of slit2 and miR-218, and a general correlation among tbx5, slit2, slit3 and miR-218 expression (Fig. S2). [score:7]
The knockdown efficiency of these morpholinos was confirmed by their ability to down-regulate mature miR-218 (Fig. S4A), and to rescue the phenotype caused by miR-218a over -expression (Fig. S4B). [score:7]
miR-218 and Robo1 are supposed to be upregulated and downregulated, respectively, when myocardial cell migration is about to end. [score:7]
Therefore it is likely that modulation of Tbx5 in general, and over -expression of miR-218 as a consequence of Tbx5 up-regulation in particular, might have a higher impact on CHD population than previously hypothesized. [score:6]
In this view, Tbx5 mis -expression by mRNA microinjection at the one-cell stage might speed up the up-regulation of miR-218 and reduce the migration of myocardial cells precociously, which in turn might affect heart morphogenesis by impairing the correct interaction between myocardial and endocardial cells. [score:6]
Tbx5 Over -expression can be Rescued by Down-regulation of miR-218. [score:6]
Therefore our data showing a migration delay of cmlc2 -positive cardiac precursors in embryos over -expressing miR-218 (Fig. 4), but not in embryos in which miR-218 was down-regulated by MO-218 injection (Fig. 4C), are in line with these findings. [score:6]
We confirmed a correlation between tbx5 and miR-218 expression and showed that alterations of miR-218 expression have a significant impact on zebrafish heart development. [score:6]
Down-regulation of miR-218 can rescue the defects generated by tbx5 over -expression. [score:6]
This hypothesis is supported by the observation that miR-218 down-regulation by MO-218a injection rescues the effects of Tbx5 over -expression (Fig. 6). [score:6]
We reasoned that if the phenotype induced by Tbx5 over -expression was due, at least in part, to increased expression of miR-218, the co-injection of MO-218 should rescue the Tbx5 gain of function phenotype. [score:5]
The apparent lack of phenotype that we observed after MO-218a injection (Fig. 2D,I) and the very low expression of miR-218 at early developmental stages, suggest that decreased miR-218a should not contribute to the phenotype generated by Tbx5 knockdown. [score:5]
This result strengthened our hypothesis that the effect of Tbx5 over -expression on heart development might, at least in part, be be mediated by miR-218. [score:4]
Overall, these observations suggest that Tbx5 over -expression affects heart and eye development and that this might be at least partially mediated by miR-218. [score:4]
miR-218 over -expression affects cardiac development. [score:4]
All together these data indicate that correct expression of miR-218 is crucial for proper cardiac development. [score:4]
Moreover, we showed that Tbx5 deregulation affects miR-218 expression. [score:4]
org); ii) the miR-218-1 host gene, slit2, is highly sensitive to Tbx5 mis -expression [8]; iii) the secreted Slit ligands, together with their Robo receptors, contribute to the control of oriented cell tissue growth during chamber morphogenesis of the mammalian heart [18]; iv) Slit/ miR-218/Robo are part of a regulatory loop required during heart tube formation in zebrafish [16]. [score:4]
This is inconsistent with both our data and with the results of Fish et al. [16] who observed that Robo1 knock-down generates the same phenotype, because the same authors also showed that Robo1 is targeted by miR-218. [score:4]
tbx5 and miR-218 are Co-expressed in Mouse Tissues and in Cardiomyocyte Differentiation of P19CL6 Cells. [score:3]
Even after injection of high miR-218 doses, cardia bifida was never observed, suggesting that miR-218 over -expression slows down but does not arrest the migration of cardiomyocytes to the midline. [score:3]
miR-218 has also been shown to affect cancer progression by inhibiting tumor cell migration and metastasis via the repression of the Slit2/Robo1 pathway in gastric [40] and in nasopharyngeal [39] tumors, respectively. [score:3]
It is interesting to know that Pax2, that is negatively controlled by Tbx5 [45], is a predicted target of miR-218. [score:3]
robo1 has been identified as a target of miR-218 in many different organs and tissues [19], [39], [41]. [score:3]
miR-218 over -expression causes a delay in early heart field migration. [score:3]
On the other hand, tbx5 silencing, the effect of which was highest 2 days after silencing (6th day in culture, see ), caused significant reduction of slit2 and miR-218 expression 4 days after transfection (8th day in culture, Fig. 1D). [score:3]
tbx5 and miR-218 are co-expressed in cardiomyocyte differentiation of P19CL6 cells. [score:3]
miR-218 Over -expression Decreases the Migration of Myocardial Precursors. [score:3]
Pre-miRNA 218-1 expression paralleled the increase in miR-218 level during cardiomyocyte differentiation (Fig. S3A) and after Tbx5 modulation (Fig. S3B). [score:3]
Figure S7 miR-218 targets the 3′ UTR of robo1 in zebrafish embryos. [score:3]
B, qRT-PCR analysis of t bx5, slit2, slit3 and miR-218 relative expression in either expanding (GM) or differentiating (8,10,12 days) P19CL6 cells. [score:3]
Figure S2 tbx5 and miR-218 are co-expressed in mouse tissues. [score:3]
We showed a functional relation between Tbx5, Slit2 and miR-218 in P19CL6 cells in which a progressive increase of Tbx5, Slit2 and miR-218 expression was observed during cardiomyocyte differentiation. [score:3]
However miR-218b, an intergenic miRNA, has very low expression, suggesting that its contribution to the global miR-218 level might be irrelevant [16]. [score:3]
Figure S3 Expression of pre-miR-218-1 parallels that of mature miR-218 during mouse differentiation and tbx5 modulation. [score:3]
To demonstrate that the Tbx5/ miR-218 regulatory circuit is also functional during development, we used the zebrafish as a mo del system. [score:3]
A progressive increase in tbx5 expression was also observed (Fig. 1B), which was paralleled by an increase in slit2, slit3 and miR-218 transcripts. [score:3]
Figure S5 miR-218 dysregulation does not affect vascular integrity. [score:2]
To assess whether there are functional regulatory interactions among Tbx5, Slit2 and miR-218, we first examined these genes in an in vitro mo del for cardiomyocyte differentiation. [score:2]
In mice, it has been shown that miR-218 regulates vascular patterning by modulating Slit-Robo signaling [19]. [score:2]
In line with the hypothesis that miR-218 might be a Tbx5 effector, we demonstrated that miR-218a deregulation generates cardiac defects (Fig. 2A). [score:2]
Our data suggest that the haplo-insufficiency of the Tbx5 gene, at the moment the most significant cause of HOS, does not impact heart and upper limb formation through miR-218 misregulation. [score:2]
The simplest explanation for this might be that other key RNAs controlled by Tbx5 than miR-218 might be necessary for heart morphogenesis by regulating mechanisms other than myocardial cell migration. [score:2]
Our data show that miR-218 is part of a regulatory circuit through which Tbx5 controls heart morphogenesis. [score:2]
To analyze the role of miR-218 in heart development, we decided to use zebrafish since this mo del is particularly informative for studying cardiac early patterning networks due to its relatively simple two-chambered heart coupled with its ability to develop even in the absence of a functioning heart. [score:2]
We focused our attention on miR-218 since: i) it is conserved from human to zebrafish (www. [score:1]
The total numbers of embryos analyzed were as follows: Ct miRNA (1 ng) n = 293; miR-214 mimic (1 ng) n = 104; miR-492 mimic (1 ng) n = 103; miR-218 mimic (35 pg) n = 107; miR-218 mimic (135 pg) n = 180; miR-218 mimic (260 pg) n = 318; miR-218 mimic (2 ng) n = 180; MO-Ct (8 ng) n = 207; MO [D]-218 (12 ng) n = 323; MO [M]-218 (2 ng) n = 112; MO [M]-218 (4 ng) n = 165; MO [M]-218 (8 ng) n = 182. [score:1]
In zebrafish, as in mammals, two isoforms of miR-218, miR-218a-1 and miR-218a-2, are embedded in slit3 and slit2 genes, respectively. [score:1]
The authors showed that miR-218 -driven repression of Robo1/2 and of heparan sulfate proteoglycans (HSPGs), which are proteins essential for Slit/Robo signaling, negatively affects endothelial cell (EC) migration. [score:1]
At the moment we do not know how miR-218 might also partially rescue eye defects. [score:1]
Confocal images of representative 72 hpf Tg(flk1:eGFP) embryos injected with 260 pg of miR-Ct (A), 260 pg of miR-218 mimic (B) or 8 ng MO [D]-218 (C). [score:1]
A negative role of miR-218 on cell migration has been highlighted in different biological contexts. [score:1]
C, Q-RT-PCR detection of slit2 and mature miR-218 in P19CL6 cells transfected with a mix of two siRNAs against slit2 or with a siRNA-Ct. [score:1]
A third genomic copy of this miRNA, miR-218b, is present in fish. [score:1]
C,D, phenotypes induced at 72 hpf by increasing doses of miR-218 mimic (C) or MO [M]/MO [D]-218 (D) injection. [score:1]
The anti-DIG antibody-alkaline phosphatase Fab fragment was diluted 1∶4.000 in MABlock buffer (2% Blocking reagent in 100 mM Maleic acid and 150 mM NaCl) and incubation was performed at +4°C for gene probes and at room temperature for miR-218 probe. [score:1]
Whole mount in situ hybridization was performed as previously described [53] with some modification: pre-hybridization temperature was 62°C; hybridization temperature was 62°C for gene probes and 52°C for miR-218 probe. [score:1]
A-D, relative expression of tbx5, slit2, slit3 and miR-218 as evaluated by q-RT-PCR in different newborn mouse tissues. [score:1]
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2
[+] score: 15
miR-155 and miR-218 backbones lead to potent knockdownpME -RNAi651, pME -RNAi661 and pME -RNAi671 constructs with green fluorescent protein (GFP) marker followed by a synthetic pre-miR directed against the 3′-UTR of mCherry were cloned downstream of the ubiquitin promoter in a mini-tol2-R4R2 multisite gateway-compatible destination plasmid (Supplementary Fig. 3). [score:3]
hsa-miR218 -based plasmids: An artificial miRNA -expressing hsa-miR218 cassette was generated in our laboratory. [score:3]
However, the backbone based on dre-miR30 achieved only weak red fluorescence inhibition compared with mmu-miR155 or hsa-miR218 backbones. [score:2]
miR-155 and miR-218 backbones lead to potent knockdown. [score:2]
According to the cell-specific observations above, miR218 and miR155 backbones led to potent global knockdown with ∼74 and 83% reduction in red fluorescence, respectively, while the miR30 backbone reduced fluorescence modestly by ∼33%. [score:2]
Pri-hsa-miR218-2 was amplified and cloned into pME -RNAi651 in two steps to allow the insertion of a 2 × BsmBI repeat at the pre-miR218 position (Fig. 1). [score:1]
The third plasmid, based on an hsa-miR218 sequence, was made in our laboratory. [score:1]
pME -RNAi651 is based on a mmu-miR155 backbone, pME -RNAi661 on a dre-miR30 backbone and pME -RNAi671 on a hsa-miR218 backbone. [score:1]
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3
[+] score: 12
[53] [,] [71] [,] [72] miR-218 knock-down in zebrafish results in a phenotype similar to robo1 overexpression, suggesting functional regulation of Slit–Robo signalling by miR-218. [score:5]
Additionally, cross-talk was found between Robo1, Vegfa, and the Vegfr2 receptor to control heart field migration, indicating a Slit/miR-218/Robo/Vegf feedback regulatory loop regulating heart field migration. [score:3]
[71] miR-218 is able to repress expression of both robo1 and robo2 mRNA. [score:3]
Microrna-218 regulates vascular patterning by modulation of Slit-Robo signaling. [score:1]
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4
[+] score: 5
Since miR-23 (JX994633), miR-218 (JX994383) and miR-338 (JX994406) are present in the elephant shark, these conserved miRNAs are likely to be involved in the regulation of Runx2 expression in elephant shark, possibly during chondrogenic differentiation through mechanisms similar to that in other jawed vertebrates. [score:4]
Of these, binding sites for miR-23, miR-218 and miR-338 were found conserved in the 3′UTR of elephant shark Runx2, while only that for miR-28 is present in zebrafish and fugu Runx2 (Fig. 8B). [score:1]
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5
[+] score: 4
Several other miRNA clusters including miR-126, miR-218, miR-23/27 clusters are documented in the regulation of angiogenesis [39, 42– 44], whether, all these families of miRNAs function independently or in concert are unclear. [score:2]
An earlier study has demonstrated the role of miR-218 in vascular patterning by modulating Robo-Slit signaling [39]. [score:1]
MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling. [score:1]
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6
[+] score: 4
In fact, we proved that in mouse cardiac cells and zebrafish embryos, Tbx5 is able to regulate several miRNAs and, in particular, miR-218 and miR-19 (Chiavacci et al., 2012, 2015). [score:2]
A slit/miR-218/robo regulatory loop is required during heart tube formation in zebrafish. [score:2]
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