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

Item Type:Article
Title:The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection
Creators Name:Rosa, A. and Spagnoli, F.M. and Brivanlou, A.H.
Abstract: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.
Keywords:DEVBIO, RNA, Base Sequence, Body Patterning, Cell Lineage, Nonmammalian Embryo, Embryonic Development, Embryonic Stem Cells, Endoderm, Developmental Gene Expression Regulation, Left-Right Determination Factors, Mesoderm, MicroRNAs, Molecular Sequence Data, Antisense Oligonucleotides, Embryonic Organizers, Species Specificity, Xenopus Proteins, Animals, Xenopus laevis
Source:Developmental Cell
Publisher:Cell Press
Page Range:517-527
Date:21 April 2009
Official Publication:https://doi.org/10.1016/j.devcel.2009.02.007
PubMed:View item in PubMed

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