Abstract
MicroRNAs (miRNAs) are an abundant class of gene regulatory molecules (reviewed in refs 1, 2). Although computational work indicates that miRNAs repress more than a third of human genes, their roles in vertebrate development are only now beginning to be determined. Here we show that miR-196 acts upstream of Hoxb8 and Sonic hedgehog (Shh) in vivo in the context of limb development, thereby identifying a previously observed but uncharacterized inhibitory activity that operates specifically in the hindlimb. Our data indicate that miR-196 functions in a fail-safe mechanism to assure the fidelity of expression domains that are primarily regulated at the transcriptional level, supporting the idea that many vertebrate miRNAs may function as a secondary level of gene regulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Chick Embryo
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Down-Regulation / drug effects
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Extremities / embryology*
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics*
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Hedgehog Proteins
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Organ Specificity
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Ribonuclease III / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
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Tretinoin / pharmacology
Substances
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Hedgehog Proteins
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Homeodomain Proteins
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Hoxb8 protein, mouse
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MicroRNAs
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Shh protein, mouse
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Trans-Activators
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Tretinoin
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Ribonuclease III