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Originally published in Science Express on 17 March 2005
Science 6 May 2005:
Vol. 308. no. 5723, pp. 833 - 838
DOI: 10.1126/science.1109020
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Research Articles

MicroRNAs Regulate Brain Morphogenesis in Zebrafish

Antonio J. Giraldez,1* Ryan M. Cinalli,1 Margaret E. Glasner,2{dagger} Anton J. Enright,3 J. Michael Thomson,4 Scott Baskerville,2 Scott M. Hammond,4 David P. Bartel,2 Alexander F. Schier1*

MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed 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.

1 Developmental Genetics Program, Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
2 Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
3 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
4 Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Published online 17 March 2005

Include this information when citing this paper.

{dagger} Present address: Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Box 2240, San Francisco, CA 94143-2240, USA.

* To whom correspondence should be addressed. E-mail: schier{at}saturn.med.nyu.edu (A.F.S.); giraldez{at}saturn.med.nyu.edu (A.J.G.)

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