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

C Leucht, C Stigloher, A Wizenmann, R Klafke… - Nature …, 2008 - nature.com
C Leucht, C Stigloher, A Wizenmann, R Klafke, A Folchert, L Bally-Cuif
Nature neuroscience, 2008nature.com
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 …
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.
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