The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection

Dev Cell. 2009 Apr;16(4):517-27. doi: 10.1016/j.devcel.2009.02.007.


The role of microRNAs in embryonic cell fate specification is largely unknown. In vertebrates, the miR-430/427/302 family shows a unique expression signature and is exclusively expressed during early embryogenesis. Here, we comparatively address the embryonic function of miR-302 in human embryonic stem cells (hESCs) and its ortholog miR-427 in Xenopus laevis. Interestingly, we found that this miRNA family displays species-specific target selection among ligands of the Nodal pathway, with a striking conservation of the inhibitors, Lefties, but differential targeting of the activators, Nodals. The Nodal pathway plays a crucial role in germ layer specification. Accordingly, by gain and loss of function experiments in hESCs, we show that miR-302 promotes the mesendodermal lineage at the expense of neuroectoderm formation. Similarly, depletion of miR-427 in Xenopus embryos hinders the organizer formation and leads to severe dorsal mesodermal patterning defects. These findings suggest a crucial role for the miR-430/427/302 family in vertebrate embryogenesis by controlling germ layer specification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning* / drug effects
  • Cell Lineage* / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / drug effects
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Endoderm / cytology*
  • Endoderm / drug effects
  • Endoderm / embryology
  • Endoderm / metabolism
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Left-Right Determination Factors / metabolism
  • Mesoderm / cytology*
  • Mesoderm / drug effects
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • Organizers, Embryonic / cytology
  • Organizers, Embryonic / drug effects
  • Organizers, Embryonic / embryology
  • Species Specificity
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics


  • Left-Right Determination Factors
  • MIRN302A microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Xenopus Proteins