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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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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Drosophila lacking microRNA miR-278 are defective in energy homeostasis..
A. A. Teleman and S. M. Cohen (2006)
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   Abstract »    Full Text »    PDF »
Reciprocal actions of REST and a microRNA promote neuronal identity.
C. Conaco, S. Otto, J.-J. Han, and G. Mandel (2006)
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   Abstract »    Full Text »    PDF »
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I. J. MacRae, K. Zhou, F. Li, A. Repic, A. N. Brooks, W. Z. Cande, P. D. Adams, and J. A. Doudna (2006)
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   Abstract »    Full Text »    PDF »
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E. M. Adler, N. R. Gough, and L. B. Ray (2006)
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   Abstract »    Full Text »    PDF »
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W. P. Kloosterman, F. A. Steiner, E. Berezikov, E. de Bruijn, J. van de Belt, M. Verheul, E. Cuppen, and R. H.A. Plasterk (2006)
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   Abstract »    Full Text »    PDF »
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E. Maniataki and Z. Mourelatos (2005)
Genes & Dev. 19, 2979-2990
   Abstract »    Full Text »    PDF »
Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development.
A. A. Aboobaker, P. Tomancak, N. Patel, G. M. Rubin, and E. C. Lai (2005)
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   Abstract »    Full Text »    PDF »
MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function.
D. T. Humphreys, B. J. Westman, D. I. K. Martin, and T. Preiss (2005)
PNAS 102, 16961-16966
   Abstract »    Full Text »    PDF »
microPrimer: the biogenesis and function of microRNA.
T. Du and P. D. Zamore (2005)
Development 132, 4645-4652
   Abstract »    Full Text »    PDF »
MicroRNA functions in animal development and human disease.
I. Alvarez-Garcia and E. A. Miska (2005)
Development 132, 4653-4662
   Abstract »    Full Text »    PDF »
Camels and zebrafish, viruses and cancer: a microRNA update.
E. Berezikov and R. H.A. Plasterk (2005)
Hum. Mol. Genet. 14, R183-R190
   Abstract »    Full Text »    PDF »
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J. Brennecke, A. Stark, and S. M. Cohen (2005)
Genes & Dev. 19, 2261-2264
   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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E. P. Murchison, J. F. Partridge, O. H. Tam, S. Cheloufi, and G. J. Hannon (2005)
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   Abstract »    Full Text »    PDF »
The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb.
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   Abstract »    Full Text »    PDF »
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E. Wienholds, W. P. Kloosterman, E. Miska, E. Alvarez-Saavedra, E. Berezikov, E. de Bruijn, H. R. Horvitz, S. Kauppinen, and R. H. A. Plasterk (2005)
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   Abstract »    Full Text »    PDF »
The developmental miRNA profiles of zebrafish as determined by small RNA cloning.
P. Y. Chen, H. Manninga, K. Slanchev, M. Chien, J. J. Russo, J. Ju, R. Sheridan, B. John, D. S. Marks, D. Gaidatzis, et al. (2005)
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