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

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

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Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, United Kingdom.


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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