TY - JOUR
T1 - Inhibition of microRNA suppression of dishevelled results in Wnt pathway-associated developmental defects in sea urchin
AU - Sampilo, Nina Faye
AU - Stepicheva, Nadezda A.
AU - Zaidi, Syed Aun Murtaza
AU - Wang, Lingyu
AU - Wu, Wei
AU - Wikramanayake, Athula
AU - Song, Jia L.
N1 - Funding Information:
This work is funded by a National Institutes of Health National Institute of General Medical Sciences grant (5P20GM103653-02-Delaware INBRE), a National Science Foundation CAREER award (IOS 1553338 to J.L.S.) and a National Science Foundation grant (IOS 0754323 to A.W.). Deposited in PMC for release after 12 months.
PY - 2018/12
Y1 - 2018/12
N2 - 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 dosedependent 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.
AB - 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 dosedependent 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.
KW - Cilia
KW - MiRNA target protector
KW - Post-transcriptional regulation
KW - Primary mesenchyme cells
KW - Sea urchin
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U2 - 10.1242/dev.167130
DO - 10.1242/dev.167130
M3 - Article
C2 - 30389855
AN - SCOPUS:85058062950
VL - 145
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 23
M1 - dev167130
ER -