MicroRNAs Regulate Brain Morphogenesis in Zebrafish

MicroRNAs (miRNAs) are small RNAs that regulate gene expression post-transcriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer RNaseIII and dsRNA-binding domains. Mutant embryos do not process precursor-miRNAs into mature miRNAs, but injection of pre-processed miRNAs restores gene silencing, indicating that the disrupted domains are dispensable for later steps in silencing. MZdicer mutants undergo axis formation and differentiate multiple cell types but display abnormal morphogenesis during gastrulation, brain formation, somitogenesis and heart development. Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNAs during morphogenesis.