miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2

Blood. 2009 Feb 19;113(8):1794-804. doi: 10.1182/blood-2008-05-155812. Epub 2008 Oct 10.


We demonstrate that in zebrafish, the microRNA miR-451 plays a crucial role in promoting erythroid maturation, in part via its target transcript gata2. Zebrafish miR-144 and miR-451 are processed from a single precursor transcript selectively expressed in erythrocytes. In contrast to other hematopoietic mutants, the zebrafish mutant meunier (mnr) showed intact erythroid specification but diminished miR-144/451 expression. Although erythropoiesis initiated normally in mnr, erythrocyte maturation was morphologically retarded. Morpholino knockdown of miR-451 increased erythrocyte immaturity in wild-type embryos, and miR-451 RNA duplexes partially rescued erythroid maturation in mnr, demonstrating a requirement and role for miR-451 in erythrocyte maturation. mnr provided a selectively miR-144/451-deficient background, facilitating studies to discern miRNA function and validate candidate targets. Among computer-predicted miR-451 targets potentially mediating these biologic effects, the pro-stem cell transcription factor gata2 was an attractive candidate. In vivo reporter assays validated the predicted miR-451/gata2-3'UTR interaction, gata2 down-regulation was delayed in miR-451-knockdown and mnr embryos, and gata2 knockdown partially restored erythroid maturation in mnr, collectively confirming gata2 down-regulation as pivotal for miR-451-driven erythroid maturation. These studies define a new genetic pathway promoting erythroid maturation (mnr/miR-451/gata2) and provide a rare example of partial rescue of a mutant phenotype solely by miRNA overexpression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cell Differentiation / physiology
  • Erythrocytes / cytology*
  • Erythroid Cells / cytology*
  • Erythropoiesis / genetics*
  • GATA2 Transcription Factor / genetics*
  • Gene Expression Regulation, Developmental
  • MicroRNAs / genetics*
  • Mutagenesis
  • Phenotype
  • RNA, Messenger / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics*


  • GATA2 Transcription Factor
  • Gata2a protein, zebrafish
  • MicroRNAs
  • Mirn451 microRNA, zebrafish
  • RNA, Messenger
  • Zebrafish Proteins