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

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.

Pubmed ID: 22160706

Authors

  • Agostini M
  • Tucci P
  • Steinert JR
  • Shalom-Feuerstein R
  • Rouleau M
  • Aberdam D
  • Forsythe ID
  • Young KW
  • Ventura A
  • Concepcion CP
  • Han YC
  • Candi E
  • Knight RA
  • Mak TW
  • Melino G

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

December 27, 2011

Associated Grants

  • Agency: Telethon, Id: GGP09133
  • Agency: Medical Research Council, Id: MC_U132670600

Mesh Terms

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