ZFIN ID: ZDB-PUB-080506-8
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.
Date: 2008
Source: Nature Neuroscience   11(6): 641-648 (Journal)
Registered Authors: Bally-Cuif, Laure, Folchert, Anja, Leucht, Christoph, Stigloher, Christian
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/physiology
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian
  • Fibroblast Growth Factors/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/physiology*
  • Mesencephalon/embryology*
  • MicroRNAs/pharmacology
  • MicroRNAs/physiology*
  • Nerve Tissue Proteins/metabolism
  • Numerical Analysis, Computer-Assisted
  • Organizers, Embryonic/physiology*
  • Promoter Regions, Genetic/physiology
  • Rhombencephalon/embryology*
  • Signal Transduction/drug effects
  • Signal Transduction/physiology
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
PubMed: 18454145 Full text @ Nat. Neurosci.
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.