ECB-ART-46731
Development
2018 Nov 30;14523:. doi: 10.1242/dev.167130.
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Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin.
Sampilo NF
,
Stepicheva NA
,
Zaidi SAM
,
Wang L
,
Wu W
,
Wikramanayake A
,
Song JL
.
Abstract
MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expressions by binding to the 3'' untranslated region of target mRNAs thereby silencing translation. Some miRNAs are key regulators of the Wnt signaling pathways, which impact developmental processes. This study investigates miRNA regulation of different isoforms of Dishevelled (Dvl/Dsh), which encode a key component in the Wnt signaling pathway. The sea urchin Dvl mRNA isoforms have similar spatial distribution in early development, but one isoform is distinctively expressed in the larval ciliary band. We demonstrated that Dvl isoforms are directly suppressed by miRNAs. By blocking miRNA suppression of Dvl isoforms, we observed dose-dependent defects in spicule length, patterning of the primary mesenchyme cells, gut morphology, and cilia. These defects likely result from increased Dvl protein levels, leading to perturbation of Wnt-dependent signaling pathways and additional Dvl-mediated processes. We further demonstrated that overexpression of Dvl isoforms recapitulated some of the Dvl miRNATP-induced phenotypes. Overall, our results indicate that miRNA suppression of Dvl isoforms plays an important role in ensuring proper development and function of primary mesenchyme cells and cilia.
PubMed ID: 30389855
PMC ID: PMC6288383
Article link: Development
Grant support: [+]
P20 GM103653 NIGMS NIH HHS
Genes referenced: impact LOC100887844 LOC584189 LOC594566
Morpholinos: LOC584189 MO3 LOC584189 MO4 LOC584189 MO5
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