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

By 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 and Gerry Melino


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

Topics: Biological Sciences
Publisher: National Academy of Sciences
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Provided by: PubMed Central
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