PUBLICATION
MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary
- Authors
- Leucht, C., Stigloher, C., Wizenmann, A., Klafke, R., Folchert, A., and Bally-Cuif, L.
- ID
- ZDB-PUB-080506-8
- 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.
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping