|ZFIN ID: ZDB-PUB-080506-8|
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MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary
Leucht, C., Stigloher, C., Wizenmann, A., Klafke, R., Folchert, A., and Bally-Cuif, L.
|Source:||Nature Neuroscience 11(6): 641-648 (Journal)|
|Registered Authors:||Bally-Cuif, Laure, Folchert, Anja, Leucht, Christoph, Stigloher, Christian|
|PubMed:||18454145 Full text @ Nat. Neurosci.|
Leucht, C., Stigloher, C., Wizenmann, A., Klafke, R., Folchert, A., and Bally-Cuif, L. (2008) MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nature Neuroscience. 11(6):641-648.
ABSTRACTThe 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.