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microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons

Nature Neuroscience volume 15, pages 697699 (2012) | Download Citation

Abstract

The capacity of neurons to develop a long axon and multiple dendrites defines neuron connectivity in the CNS. The highly conserved microRNA-9 (miR-9) is expressed in both neuronal precursors and some post-mitotic neurons, and we detected miR-9 expression in the axons of primary cortical neurons. We found that miR-9 controlled axonal extension and branching by regulating the levels of Map1b, an important protein for microtubule stability. Following microfluidic separation of the axon and the soma, we found that miR-9 repressed Map1b translation and was a functional target for the BDNF-dependent control of axon extension and branching. We propose that miR-9 links regulatory signaling processes with dynamic translation mechanisms, controlling Map1b protein levels and axon development.

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Acknowledgements

The Wellcome Trust (090868, N.P.; GR083272, B.B.), and Medical Research Council (grant G0900584, F.D.-B., P.S. and N.P.; institutional funds, P.G., F.G.) funded this work.

Author information

Affiliations

  1. Faculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester, UK.

    • Federico Dajas-Bailador
    • , Boyan Bonev
    • , Peter Stanley
    •  & Nancy Papalopulu
  2. Division of Molecular Neurobiology, National Institute for Medical Research, London, UK.

    • Patricia Garcez
    •  & Francois Guillemot

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Contributions

F.D.-B. devised, performed and analyzed most of the experiments. B.B. discussed the project, made all of the luciferase and dGFP constructs and performed the luciferase and PCR experiments. P.G. and F.G. performed the in utero electroporation experiments. P.S. carried out the FISH experiments. N.P. supervised the project and wrote the manuscript with F.D.-B.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Federico Dajas-Bailador or Nancy Papalopulu.

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DOI

https://doi.org/10.1038/nn.3082

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