MicroRNA-34a Regulates Neurite Outgrowth, Spinal Morphology, and Function

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Dec 14

PMID 22160706

Citations 130

Authors

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

Affiliations

Soon will be listed here.

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.

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