Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: miR-9 is localized in the axons of cortical neurons and regulates their development.
Figure 2: miR-9 targets Map1b and controls axon growth locally.
Figure 3: miR-9 regulates axon development in vivo and responds to BDNF signaling.

Similar content being viewed by others

References

  1. Barnes, A.P. & Polleux, F. Annu. Rev. Neurosci. 32, 347–381 (2009).

    Article  CAS  Google Scholar 

  2. Hengst, U., Deglincerti, A., Kim, H.J., Jeon, N.L. & Jaffrey, S.R. Nat. Cell Biol. 11, 1024–1030 (2009).

    Article  CAS  Google Scholar 

  3. Gibson, D.A. & Ma, L. Development 138, 183–195 (2011).

    Article  CAS  Google Scholar 

  4. Natera-Naranjo, O., Aschrafi, A., Gioio, A.E. & Kaplan, B.B. RNA 16, 1516–1529 (2010).

    Article  CAS  Google Scholar 

  5. Olsson-Carter, K. & Slack, F.J. PLoS Genet. 6, e1001054 (2010).

    Article  Google Scholar 

  6. Baudet, M.-L. et al. Nat. Neurosci. 15, 29–38 (2012).

    Article  CAS  Google Scholar 

  7. Gao, F.-B. Neural Dev. 5, 25 (2010).

    Article  Google Scholar 

  8. Bonev, B., Pisco, A. & Papalopulu, N. Dev. Cell 20, 19–32 (2011).

    Article  CAS  Google Scholar 

  9. Bouquet, C. et al. J. Neurosci. 24, 7204–7213 (2004).

    Article  CAS  Google Scholar 

  10. Montenegro-Venegas, C. et al. Mol. Biol. Cell 21, 3518–3528 (2010).

    Article  CAS  Google Scholar 

  11. Black, M.M., Slaughter, T. & Fischer, I. J. Neurosci. 14, 857–870 (1994).

    Article  CAS  Google Scholar 

  12. Hoshino, N., Vatterott, P., Egwiekhor, A. & Rochlin, M.W. Dev. Neurosci. 32, 184–196 (2010).

    Article  CAS  Google Scholar 

  13. Panagiotaki, N., Dajas-Bailador, F., Amaya, E., Papalopulu, N. & Dorey, K. Development 137, 4005–4015 (2010).

    Article  CAS  Google Scholar 

  14. Ji, Y. et al. Nat. Neurosci. 13, 302–309 (2010).

    Article  CAS  Google Scholar 

  15. Santos, A.R., Comprido, D. & Duarte, C.B. Prog. Neurobiol. 92, 505–516 (2010).

    Article  CAS  Google Scholar 

  16. Dajas-Bailador, F., Jones, E.V. & Whitmarsh, A.J. Curr. Biol. 18, 221–226 (2008).

    Article  CAS  Google Scholar 

  17. Gordon-Weeks, P.R. & Fischer, I. Microsc. Res. Tech. 48, 63–74 (2000).

    Article  CAS  Google Scholar 

  18. Bastian, I. et al. Histochem. Cell Biol. 135, 37–45 (2011).

    Article  CAS  Google Scholar 

  19. Pacary, E. et al. Neuron 69, 1069–1084 (2011).

    Article  CAS  Google Scholar 

  20. Xu, X.-L., Li, Y., Wang, F. & Gao, F.-B. J. Neurosci. 28, 11883–11889 (2008).

    Article  CAS  Google Scholar 

  21. Dent, E.W., Barnes, A.M., Tang, F. & Kalil, K. J. Neurosci. 24, 3002–3012 (2004).

    Article  CAS  Google Scholar 

  22. Jeanneteau, F., Deinhardt, K., Miyoshi, G., Bennett, A.M. & Chao, M.V. Nat. Neurosci. 13, 1373–1379 (2010).

    Article  CAS  Google Scholar 

Download references

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

Authors and Affiliations

Authors

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.

Corresponding authors

Correspondence to Federico Dajas-Bailador or Nancy Papalopulu.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 (PDF 3635 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dajas-Bailador, F., Bonev, B., Garcez, P. et al. microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons. Nat Neurosci 15, 697–699 (2012). https://doi.org/10.1038/nn.3082

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing