PUBLICATION

miR-9 Controls the Timing of Neurogenesis through the Direct Inhibition of Antagonistic Factors

Authors
Coolen, M., Thieffry, D., Drivenes, O., Becker, T.S., and Bally-Cuif, L.
ID
ZDB-PUB-120522-10
Date
2012
Source
Developmental Cell   22(5): 1052-1064 (Journal)
Registered Authors
Bally-Cuif, Laure, Becker, Thomas S., Drivenes, Oyvind
Keywords
none
MeSH Terms
  • Alanine/analogs & derivatives
  • Alanine/pharmacology
  • Animals
  • Azepines/pharmacology
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Cycle/genetics
  • Cell Cycle/physiology*
  • Cell Differentiation/physiology
  • DNA-Binding Proteins/metabolism
  • ELAV Proteins/metabolism
  • ELAV-Like Protein 3
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Neurogenesis/genetics
  • Neurogenesis/physiology*
  • Neurons/cytology
  • Neurons/physiology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism
PubMed
22595676 Full text @ Dev. Cell
Abstract

The timing of commitment and cell-cycle exit within progenitor populations during neurogenesis is a fundamental decision that impacts both the number and identity of neurons produced during development. We show here that microRNA-9 plays a key role in this process through the direct inhibition of targets with antagonistic functions. Across the ventricular zone of the developing zebrafish hindbrain, miR-9 expression occurs at a range of commitment stages. Abrogating miR-9 function transiently delays cell-cycle exit, leading to the increased generation of late-born neuronal populations. Target protection analyses in vivo identify the progenitor-promoting genes her6 and zic5 and the cell-cycle exit-promoting gene elavl3/HuC as sequential targets of miR-9 as neurogenesis proceeds. We propose that miR-9 activity generates an ambivalent progenitor state poised to respond to both progenitor maintenance and commitment cues, which may be necessary to adjust neuronal production to local extrinsic signals during late embryogenesis.

Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes