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Peng, C. ; Li, N.* ; Ng, Y.K. ; Zhang, J. ; Meier, F. ; Theis, F.J. ; Merkenschlager, M.* ; Chen, W.* ; Wurst, W. ; Prakash, N.

A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation.

J. Neurosci. 32, 13292-13308 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
MicroRNAs have emerged as key posttranscriptional regulators of gene expression during vertebrate development. We show that the miR-200 family plays a crucial role for the proper generation and survival of ventral neuronal populations in the murine midbrain/hindbrain region, including midbrain dopaminergic neurons, by directly targeting the pluripotency factor Sox2 and the cell-cycle regulator E2F3 in neural stem/progenitor cells. The lack of a negative regulation of Sox2 and E2F3 by miR-200 in conditional Dicer1 mutants (En1(+/Cre); Dicer1(flox/flox) mice) and after miR-200 knockdown in vitro leads to a strongly reduced cell-cycle exit and neuronal differentiation of ventral midbrain/hindbrain (vMH) neural progenitors, whereas the opposite effect is seen after miR-200 overexpression in primary vMH cells. Expression of miR-200 is in turn directly regulated by Sox2 and E2F3, thereby establishing a unilateral negative feedback loop required for the cell-cycle exit and neuronal differentiation of neural stem/progenitor cells. Our findings suggest that the posttranscriptional regulation of Sox2 and E2F3 by miR-200 family members might be a general mechanism to control the transition from a pluripotent/multipotent stem/progenitor cell to a postmitotic and more differentiated cell.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter EMBRYONIC STEM-CELLS; III ENZYME DICER; ISTHMIC ORGANIZER; CEREBELLUM DEVELOPMENT; DOPAMINERGIC-NEURONS; RNA INTERFERENCE; MAMMALIAN-CELLS; GENE-EXPRESSION; MOUSE-BRAIN; MIDBRAIN
ISSN (print) / ISBN 0270-6474
e-ISSN 1529-2401
Zeitschrift Journal of Neuroscience
Quellenangaben Band: 32, Heft: 38, Seiten: 13292-13308 Artikelnummer: , Supplement: ,
Verlag Society for Neuroscience
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Bioinformatics and Systems Biology (IBIS)
CCG Molecular Neurogenetics (IDG-KMN)
Institute of Computational Biology (ICB)