The Etv2-miR-130a Network Regulates Mesodermal Specification

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14 Scopus citations

Abstract

MicroRNAs (miRNAs) are known to regulate critical developmental stages during embryogenesis. Here, we defined an Etv2-miR-130a cascade that regulates mesodermal specification and determination. Ablation of Dicer in the Etv2-expressing precursors resulted in altered mesodermal lineages and embryonic lethality. We identified miR-130a as a direct target of Etv2 and demonstrated its role in the segregation of bipotent hemato-endothelial progenitors toward the endothelial lineage. Gain-of-function experiments demonstrated that miR-130a promoted the endothelial program at the expense of the cardiac program without impacting the hematopoietic lineages. In contrast, CRISPR/Cas9-mediated knockout of miR-130a demonstrated a reduction of the endothelial program without affecting hematopoiesis. Mechanistically, miR-130a directly suppressed Pdgfra expression and promoted the endothelial program by blocking Pdgfra signaling. Inhibition or activation of Pdgfra signaling phenocopied the miR-130a overexpression and knockout phenotypes, respectively. In summary, we report the function of a miRNA that specifically promotes the divergence of the hemato-endothelial progenitor to the endothelial lineage.

Original languageEnglish (US)
Pages (from-to)915-923
Number of pages9
JournalCell reports
Volume13
Issue number5
DOIs
StatePublished - Nov 3 2015

Bibliographical note

Funding Information:
Funding support was obtained from the NIH (U01HL100407 and R01HL122576 to D.J.G. and R01AR064195 to Y.K.). The authors thank Naoyuki Tahara for his technical assistance with the zebrafish studies.

Publisher Copyright:
© 2015 The Authors.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Dicer
  • Etv2
  • Lineage specification
  • MiR-130a
  • MicroRNA

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