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

Development. 2018 Nov 30;145(23):dev167130. doi: 10.1242/dev.167130.

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.

Keywords: Cilia; Post-transcriptional regulation; Primary mesenchyme cells; Sea urchin; miRNA target protector.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning / genetics
  • Bone and Bones / drug effects
  • Bone and Bones / embryology
  • Bone and Bones / metabolism
  • Cilia / drug effects
  • Cilia / metabolism
  • Digestive System / drug effects
  • Digestive System / pathology
  • Dishevelled Proteins / chemistry
  • Dishevelled Proteins / genetics
  • Dishevelled Proteins / metabolism*
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism*
  • Embryonic Development / drug effects
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Morpholinos / pharmacology
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sea Urchins / drug effects
  • Sea Urchins / embryology*
  • Sea Urchins / genetics*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wnt Signaling Pathway* / drug effects
  • Wnt Signaling Pathway* / genetics

Substances

  • Dishevelled Proteins
  • MicroRNAs
  • Morpholinos
  • Protein Isoforms
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A