microRNA-31 regulates skeletogenesis by direct suppression of Eve and Wnt1.
microRNAs (miRNAs) play a critical role in a variety of biological processes, including embryogenesis and the physiological functions of cells. Evolutionarily conserved microRNA-31 (miR-31) has been found to be involved in cancer, bone formation, and lymphatic development. We previously discovered that, in the sea urchin, miR-31 knockdown (KD) embryos have shortened dorsoventral connecting rods, mispatterned skeletogenic primary mesenchyme cells (PMCs) and shifted and expanded Vegf3 expression domain. Vegf3 itself does not contain miR-31 binding sites; however, we identified its upstream regulators Eve and Wnt1 to be directly suppressed by miR-31. Removal of miR-31's suppression of Eve and Wnt1 resulted in skeletal and PMC patterning defects, similar to miR-31 KD phenotypes. Additionally, removal of miR-31's suppression of Eve and Wnt1 results in an expansion and anterior shift in expression of Veg1 ectodermal genes, including Vegf3 in the blastulae. This indicates that miR-31 indirectly regulates Vegf3 expression through directly suppressing Eve and Wnt1. Furthermore, removing miR-31 suppression of Eve is sufficient to cause skeletogenic defects, revealing a novel regulatory role of Eve in skeletogenesis and PMC patterning. Overall, this study provides a proposed molecular mechanism of miR-31's regulation of skeletogenesis and PMC patterning through its cross-regulation of a Wnt signaling ligand and a transcription factor of the endodermal and ectodermal gene regulatory network.
['Sampilo|Nina Faye|NF|', 'Stepicheva|Nadezda A|NA|', 'Song|Jia L|JL|']
D000818:Animals D030801:Animals, Genetically Modified D019521:Body Patterning D047108:Embryonic Development D005260:Female D018507:Gene Expression Regulation, Developmental D055785:Gene Knockdown Techniques D053263:Gene Regulatory Networks D018398:Homeodomain Proteins D008297:Male D059630:Mesenchymal Stem Cells D035683:MicroRNAs D041641:Musculoskeletal Development D010641:Phenotype D015398:Signal Transduction D047270:Strongylocentrotus purpuratus D014157:Transcription Factors D051155:Wnt1 Protein
MicroRNA-31 Sea urchin Primary mesenchyme cells Wnt Even-skipped Post-transcriptional regulation Vegf signaling miRNA target protector