microRNA-34a regulates neurite outgrowth, spinal morphology, and function

Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21099-104. doi: 10.1073/pnas.1112063108. Epub 2011 Dec 12.

Abstract

The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, we have shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is retained in mouse ES cells committed to differentiate toward a neurological phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal morphology, and results in electrophysiological changes consistent with a reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional relevance in primary neurons. These data reinforce a role for miR-34a in neuronal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Electrophysiology
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism*
  • Neurites / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Spine / cytology*
  • Spine / physiology
  • Synaptotagmin I / metabolism
  • Syntaxin 1 / metabolism

Substances

  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Nuclear Proteins
  • Synaptotagmin I
  • Syntaxin 1
  • Syt1 protein, mouse
  • delta Np73, mouse