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  • The EMBO Journal (2009) 28, 697 - 710
  • doi:10.1038/emboj.2009.10

Published online: 5 February 2009

Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levelsEMBO Open

Roberto Fiore1,a, Sharof Khudayberdiev1,a, Mette Christensen1,2, Gabriele Siegel1, Steven W Flavell3, Tae-Kyung Kim3, Michael E Greenberg3 and Gerhard Schratt1

  1. Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, Universität Heidelberg, and Institut für Neuroanatomie, Universitätsklinikum Heidelberg, Heidelberg, Germany
  2. Wilhelm Johannsen Center for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej, Denmark
  3. Department of Neurobiology, Harvard Medical School, Boston, MA, USA

Correspondence to:

Gerhard Schratt, Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, University of Heidelberg, Im Neuenheimer Feld 345, 69210 Heidelberg, Germany. Tel.: +49 6221 566210; Fax: +49 6221 567897; E-mail: schratt@ana.uni-heidelberg.de

aThese authors contributed equally to this work

Received 11 September 2008; Accepted 23 December 2008

Neuronal activity orchestrates the proper development of the neuronal circuitry by regulating both transcriptional and post-transcriptional gene expression programmes. How these programmes are coordinated, however, is largely unknown. We found that the transcription of miR379–410, a large cluster of brain-specific microRNAs (miRNAs), is induced by increasing neuronal activity in primary rat neurons. Results from chromatin immunoprecipitation and luciferase reporter assays suggest that binding of the transcription factor myocyte enhancing factor 2 (Mef2) upstream of miR379–410 is necessary and sufficient for activity-dependent transcription of the cluster. Mef2-induced expression of at least three individual miRNAs of the miR379–410 cluster is required for activity-dependent dendritic outgrowth of hippocampal neurons. One of these miRNAs, the dendritic miR-134, promotes outgrowth by inhibiting translation of the mRNA encoding for the translational repressor Pumilio2. In summary, we have described a novel regulatory pathway that couples activity-dependent transcription to miRNA-dependent translational control of gene expression during neuronal development.

  • Keywords:

    • dendritogenesis,
    • Mef2,
    • microRNA,
    • neuronal activity,
    • Pumilio

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