MicroRNA-9 reveals regional diversity of neural progenitors along the anterior-posterior axis.
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.
Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Boyan
B
Bonev
Angela
A
Pisco
Nancy
N
Papalopulu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology; D012249:Rhombencephalon / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism
C555881:MIRN9 microRNA, Xenopus; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016159:Tumor Suppressor Protein p53; D029867:Xenopus Proteins; C493963:Xicl protein, Xenopus; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27
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