Article abstract
Nature Neuroscience
Published online: 4 May 2008 | doi:10.1038/nn.2115
MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary
Christoph Leucht1,5, Christian Stigloher1,5, Andrea Wizenmann2,4, Ruth Klafke3, Anja Folchert1 & Laure Bally-Cuif1
Abstract
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.
- Department of Zebrafish Neurogenetics, Institute of Developmental Genetics, Helmholtz-Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
- Institute of Stem Cell Research, Helmholtz-Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
- Institute of Developmental Genetics, Helmholtz-Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
- Present address: Institute of Anatomy, University of Tübingen, Österbergstrasse 3, D-72074 Tübingen, Germany.
- These authors contributed equally to the work.
Correspondence to: Christoph Leucht1,5 e-mail: leucht@topforscher.de
Correspondence to: Laure Bally-Cuif1 e-mail: bally@helmholtz-muenchen.de