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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

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


  • MicroRNAs
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • Fibroblast Growth Factors