Abstract
Neural progenitors self-renew and generate neurons throughout the central nervous system. Here, we uncover an unexpected regional specificity in the properties of neural progenitor cells, revealed by the function of a microRNA--miR-9. miR-9 is expressed in neural progenitors, and its knockdown results in an inhibition of neurogenesis along the anterior-posterior axis. However, the underlying mechanism differs--in the hindbrain, progenitors fail to exit the cell cycle, whereas in the forebrain they undergo apoptosis, counteracting the proliferative effect. Among several targets, we functionally identify hairy1 as a primary target of miR-9, regulated at the mRNA level. hairy1 mediates the effects of miR-9 on proliferation, through Fgf8 signaling in the forebrain and Wnt signaling in the hindbrain, but affects apoptosis only in the forebrain, via the p53 pathway. Our findings show a positional difference in the responsiveness of progenitors to miR-9 depletion, revealing an underlying divergence of their properties.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Base Sequence
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Body Patterning / drug effects
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Body Patterning / genetics*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Embryo, Nonmammalian / cytology
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Embryo, Nonmammalian / drug effects
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Embryo, Nonmammalian / metabolism
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Gene Expression Regulation / drug effects
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Gene Knockdown Techniques
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Molecular Sequence Data
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Neural Stem Cells / cytology*
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Neural Stem Cells / drug effects
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Neural Stem Cells / metabolism
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Neurogenesis / drug effects
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Neurogenesis / genetics*
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Oligonucleotides, Antisense / pharmacology
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Organ Specificity / drug effects
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Organ Specificity / genetics*
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Phenotype
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Prosencephalon / cytology
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Rhombencephalon / cytology
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Tumor Suppressor Protein p53 / metabolism
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Xenopus / embryology
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Xenopus / genetics
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism
Substances
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MIRN9 microRNA, Xenopus
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MicroRNAs
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Oligonucleotides, Antisense
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Tumor Suppressor Protein p53
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Xenopus Proteins
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Xicl protein, Xenopus
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Cyclin D1
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Cyclin-Dependent Kinase Inhibitor p27