Inhibition of microRNA suppression of results in Wnt pathway-associated developmental defects in sea urchin.

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 (), which encode a key component in the Wnt signaling pathway. The sea urchin mRNA isoforms have similar spatial distribution in early development, but one isoform is distinctively expressed in the larval ciliary band. We demonstrated that isoforms are directly suppressed by miRNAs. By blocking miRNA suppression of 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 isoforms recapitulated some of the miRNATP-induced phenotypes. Overall, our results indicate that miRNA suppression of isoforms plays an important role in ensuring proper development and function of primary mesenchyme cells and cilia.