Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish
- Viravuth P. Yin1,
- J. Michael Thomson2,
- Ryan Thummel3,
- David R. Hyde3,
- Scott M. Hammond2, and
- Kenneth D. Poss1,4
- 1 Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA;
- 2 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
- 3 Center for Zebrafish Research and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA
Abstract
Appendage regeneration is defined by rapid changes in gene expression that achieve dramatic developmental effects, suggesting involvement of microRNAs (miRNAs). Here, we find dynamic regulation of many miRNAs during zebrafish fin regeneration. In particular, miR-133 levels are high in uninjured fins but low during regeneration. When regeneration was blocked by Fibroblast growth factor (Fgf) receptor inhibition, high miR-133 levels were quickly restored. Experimentally increasing amounts of miR-133 attenuated fin regeneration. Conversely, miR-133 antagonism during Fgf receptor inhibition accelerated regeneration through increased proliferation within the regeneration blastema. The Mps1 kinase, an established positive regulator of blastemal proliferation, is an in vivo target of miR-133. Our findings identify miRNA depletion as a new regulatory mechanism for complex tissue regeneration.
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Footnotes
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↵4 Corresponding author.
↵4 E-MAIL k.poss{at}cellbio.duke.edu; FAX (919) 684-5481.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1641808.
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- Received December 10, 2007.
- Accepted January 21, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
