ZFIN ID: ZDB-PUB-140101-23
miR-219 Regulates Neural Precursor Differentiation by Direct Inhibition of Apical Par Polarity Proteins
Hudish, L.I., Blasky, A.J., and Appel, B.
Date: 2013
Source: Developmental Cell 27(4): 387-398 (Journal)
Registered Authors: Appel, Bruce
Keywords: none
MeSH Terms:
  • Animals
  • Blotting, Western
  • Cell Cycle
  • Cell Differentiation*
  • Cell Polarity*
  • Cell Proliferation
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Luciferases/metabolism
  • MicroRNAs/genetics*
  • Neurogenesis/genetics*
  • Neurons/cytology*
  • Neurons/metabolism
  • RNA, Messenger/genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells/cytology*
  • Stem Cells/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 24239515 Full text @ Dev. Cell
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ABSTRACT

Asymmetric self-renewing division of neural precursors is essential for brain development. Partitioning-defective (Par) proteins promote self-renewal, and their asymmetric distribution provides a mechanism for asymmetric division. Near the end of neural development, most asymmetric division ends and precursors differentiate. This correlates with Par protein disappearance, but mechanisms that cause downregulation are unknown. MicroRNAs can promote precursor differentiation but have not been linked to Par protein regulation. We tested a hypothesis that microRNA miR-219 promotes precursor differentiation by inhibiting Par proteins. Neural precursors in zebrafish larvae lacking miR-219 function retained apical proteins, remained in the cell cycle, and failed to differentiate. miR-219 inhibited expression via target sites within the 32 untranslated sequence of pard3 and prkci mRNAs, which encode Par proteins, and blocking miR-219 access to these sites phenocopied loss of miR-219 function. We propose that negative regulation of Par protein expression by miR-219 promotes cell-cycle exit and differentiation.

ADDITIONAL INFORMATIONNo data available