ZFIN ID: ZDB-PUB-170214-24
MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2
Ma, H., Lin, Y., Zhao, Z.A., Lu, X., Yu, Y., Zhang, X., Wang, Q., Li, L.
Date: 2016
Source: The Journal of biological chemistry   291: 12126-35 (Journal)
Registered Authors: Li, Lei, Wang, Qiang
Keywords: SMAD transcription factor, activin, development, embryonic stem cell, germ layer specification, left-right determination factor 2 (LEFTY2), microRNA (miRNA)
MeSH Terms:
  • Animals
  • Blotting, Western
  • Cell Differentiation/genetics*
  • Cells, Cultured
  • Embryo, Mammalian/cytology
  • Embryo, Mammalian/embryology
  • Embryo, Mammalian/metabolism
  • Endoderm/cytology
  • Endoderm/embryology
  • Endoderm/metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Left-Right Determination Factors/genetics*
  • Left-Right Determination Factors/metabolism
  • Mesoderm/cytology
  • Mesoderm/embryology
  • Mesoderm/metabolism*
  • Mice
  • MicroRNAs/genetics*
  • Mouse Embryonic Stem Cells/metabolism*
  • Nodal Protein/genetics
  • Nodal Protein/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed: 27072135 Full text @ J. Biol. Chem.
Specification of the three germ layers is a fundamental process and is essential for the establishment of organ rudiments. Multiple genetic and epigenetic factors regulate this dynamic process; however, the function of specific microRNAs in germ layer differentiation remains unknown. In this study, we established that microRNA-127 (miR-127) is related to germ layer specification via microRNA array analysis of isolated three germ layers of E7.5 mouse embryos and was verified through differentiation of mouse embryonic stem cells. miR-127 is highly expressed in endoderm and primitive streak. Overexpression of miR-127 increases and inhibition of miR-127 decreases the expression of mesendoderm markers. We further show that miR-127 promotes mesendoderm differentiation through the nodal pathway, a determinative signaling pathway in early embryogenesis. Using luciferase reporter assay, left-right determination factor 2 (Lefty2), an antagonist of nodal, is identified to be a novel target of miR-127. Furthermore, the role of miR-127 in mesendoderm differentiation is attenuated by Lefty2 overexpression. Altogether, our results indicate that miR-127 accelerates mesendoderm differentiation of mouse embryonic stem cells through nodal signaling by targeting Lefty2.