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microRNA-31 regulates skeletogenesis by direct suppression of Eve and Wnt1

Nina Faye Sampilo1, Nadezda A Stepicheva2, Jia L Song1

  • 1Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA.

Developmental Biology
|January 23, 2021
PubMed

Insights

MicroRNAs (miRNAs) regulate sea urchin development by controlling skeletogenesis. MicroRNA-31 (miR-31) indirectly impacts Vegf3 expression by suppressing Eve and Wnt1, crucial for patterning primary mesenchyme cells.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators of cellular processes and development.
  • MicroRNA-31 (miR-31), an evolutionarily conserved miRNA, influences cancer, bone formation, and lymphatic development.
  • Previous studies showed miR-31 knockdown in sea urchin embryos causes defects in skeletal elements and cell patterning.

Purpose of the Study:

  • To elucidate the molecular mechanism by which miR-31 regulates skeletogenesis and primary mesenchyme cell (PMC) patterning in sea urchin embryos.
  • To investigate the indirect regulation of Vegf3 expression by miR-31 through its targets Eve and Wnt1.
  • To identify novel roles of Eve in skeletogenesis and PMC patterning.

Main Methods:

  • MicroRNA knockdown (KD) experiments in sea urchin embryos.
  • Analysis of gene expression patterns, including Vegf3, Eve, and Wnt1.
  • Investigating the regulatory relationships between miR-31, Eve, Wnt1, and Vegf3.

Main Results:

  • miR-31 KD embryos exhibit shortened connecting rods and mispatterned PMCs.
  • miR-31 directly suppresses the expression of transcription factors Eve and Wnt1.
  • Suppression of Eve and Wnt1 by miR-31 indirectly regulates Vegf3 expression, leading to developmental defects.
  • Removal of miR-31's suppression of Eve alone is sufficient to cause skeletogenic defects.

Conclusions:

  • miR-31 indirectly regulates Vegf3 expression by directly suppressing Eve and Wnt1.
  • Eve plays a novel and critical role in sea urchin skeletogenesis and PMC patterning.
  • This study reveals a molecular mechanism for miR-31-mediated regulation of skeletogenesis via cross-regulation of Wnt signaling and transcription factors.
Keywords:
Even-skippedMicroRNA-31Post-transcriptional regulationPrimary mesenchyme cellsSea urchinVegf signalingWntmiRNA target protector

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