The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection.
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.
Rosa
Alessandro
A
Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, NY 10065, USA.
Spagnoli
Francesca M
FM
Brivanlou
Ali H
AH
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D055458:Left-Right Determination Factors / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020897:Organizers, Embryonic / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D013045:Species Specificity; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
D055458:Left-Right Determination Factors; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D029867:Xenopus Proteins