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Nat Neurosci. 2008 Jun;11(6):641-8. doi: 10.1038/nn.2115. Epub 2008 May 4.

MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary.

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Department of Zebrafish Neurogenetics, Institute of Developmental Genetics, Helmholtz-Zentrum M├╝nchen, German Research Center for Environmental Health, Ingolst├Ądter Landstrasse 1, D-85764 Neuherberg, Germany.


The midbrain-hindbrain boundary (MHB) is a long-lasting organizing center in the vertebrate neural tube that is both necessary and sufficient for the ordered development of midbrain and anterior hindbrain (midbrain-hindbrain domain, MH). The MHB also coincides with a pool of progenitor cells that contributes neurons to the entire MH. Here we show that the organizing activity and progenitor state of the MHB are co-regulated by a single microRNA, miR-9, during late embryonic development in zebrafish. Endogenous miR-9 expression, initiated at late stages, selectively spares the MHB. Gain- and loss-of-function studies, in silico predictions and sensor assays in vivo demonstrate that miR-9 targets several components of the Fgf signaling pathway, thereby delimiting the organizing activity of the MHB. In addition, miR-9 promotes progression of neurogenesis in the MH, defining the MHB progenitor pool. Together, these findings highlight a previously unknown mechanism by which a single microRNA fine-tunes late MHB coherence via its co-regulation of patterning activities and neurogenesis.

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