Regulation of endoderm formation and left-right asymmetry by miR-92 during early zebrafish development

Development. 2011 May;138(9):1817-26. doi: 10.1242/dev.056697. Epub 2011 Mar 29.


microRNAs (miRNAs) are a family of 21-23 nucleotide endogenous non-coding RNAs that post-transcriptionally regulate gene expression in a sequence-specific manner. Typically, miRNAs downregulate target genes by recognizing and recruiting protein complexes to 3'UTRs, followed by translation repression or mRNA degradation. miR-92 is a well-studied oncogene in mammalian systems. Here, using zebrafish as a model system, we uncovered a novel tissue-inductive role for miR-92 during early vertebrate development. Overexpression resulted in reduced endoderm formation during gastrulation with consequent cardia and viscera bifida. By contrast, depletion of miR-92 increased endoderm formation, which led to abnormal Kupffer's vesicle development and left-right patterning defects. Using target prediction algorithms and reporter constructs, we show that gata5 is a target of miR-92. Alteration of gata5 levels reciprocally mirrored the effects of gain and loss of function of miR-92. Moreover, genetic epistasis experiments showed that miR-92-mediated defects could be substantially suppressed by modulating gata5 levels. We propose that miR-92 is a critical regulator of endoderm formation and left-right asymmetry during early zebrafish development and provide the first evidence for a regulatory function for gata5 in the formation of Kupffer's vesicle and left-right patterning.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Body Patterning / genetics*
  • Cardia / embryology
  • Cardia / metabolism
  • Embryo, Nonmammalian
  • Endoderm / embryology*
  • Endoderm / metabolism
  • GATA5 Transcription Factor / genetics
  • GATA5 Transcription Factor / metabolism
  • Gene Expression Regulation, Developmental
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Tissue Distribution
  • Viscera / embryology
  • Viscera / metabolism
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism


  • GATA5 Transcription Factor
  • MicroRNAs