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Neuronal activity controls the correct establishment and refinement of neuronal circuits by regulating key aspects such as dendritogenesis and spine development. Both transcriptional and post-transcriptional gene expression programs induced by neuronal activity have to be coordinated in a tight spatio-temporal manner in order for proper functioning of the neuron. In this context microRNAs (miRNAs), which are implicated in post-transcriptional gene regulation, are good candidates to control dendritic and spine development. In a recent study we have demonstrated that neuronal activity induces myocyte enhancing factor 2 (Mef2) dependent transcription of a large cluster of brain-specific miRNAs (miR379-410). Expression of at least three microRNAs (miR-329,-134 and -381) from this cluster is essential for activity-dependent dendritic outgrowth of hippocampal neurons. One of these three miRNAs, miR-134, promotes dendritic outgrowth by inhibiting translation of the mRNA encoding the translational regulator Pumilio2 (Pum2). In brief, our results suggest a novel role for Mef2 in promoting activity-dependent dendritogenesis by inducing the transcription of the miR379-410 cluster.