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

Massimiliano Agostini, Paola Tucci, Joern R. Steinert, Ruby Shalom-Feuerstein, Matthieu Rouleau, Daniel Aberdam, Ian D. Forsythe, Kenneth W. Young, Andrea Ventura, Carla P. Concepcion, Yoon Chi Han, Eleonora Candi, Richard A. Knight, Tak W. Mak, Gerry Melino

Research output: Contribution to journalArticlepeer-review

Abstract

The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, wehave 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.

Original languageEnglish
Pages (from-to)21099-21104
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number52
DOIs
Publication statusPublished - Dec 27 2011

Keywords

  • Cell death
  • Hippocampus
  • Neuronal differentiation
  • Synaptogenesis

ASJC Scopus subject areas

  • General

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