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Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons

Nature Cell Biology volume 13, pages 989995 (2011) | Download Citation

Abstract

During corticogenesis, pyramidal neurons (80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia1,2, and then migrate to their proper position within the cortex1,3. As pyramidal neurons migrate radially, they remain attached to their glial substrate as they pass through the subventricular and intermediate zones, regions rich in tangentially migrating interneurons and axon fibre tracts. We examined the role of lamellipodin (Lpd), a homologue of a key regulator of neuronal migration and polarization in Caenorhabditis elegans, in corticogenesis. Lpd depletion caused bipolar pyramidal neurons to adopt a tangential, rather than radial-glial, migration mode without affecting cell fate. Mechanistically, Lpd depletion reduced the activity of SRF, a transcription factor regulated by changes in the ratio of polymerized to unpolymerized actin. Therefore, Lpd depletion exposes a role for SRF in directing pyramidal neurons to select a radial migration pathway along glia rather than a tangential migration mode.

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Acknowledgements

We thank R. Treisman for providing DNA constructs and R. Hayman for help with graphics. E.M.P. was supported by an NRSA grant F32-GM074507. This work was supported by financial support from a Koch Institute Development award and NIH grant # GM068678 to F.B.G.; L-H.T. is an investigator of Howard Hughes Medical Institute.

Author information

Author notes

    • Elaine M. Pinheiro
    •  & Amy L. Norovich

    Present addresses: Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA (E.M.P.); Columbia University, New York, New York 10027, USA (A.L.N.)

Affiliations

  1. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Elaine M. Pinheiro
    • , Amy L. Norovich
    • , Marina Vidaki
    •  & Frank B. Gertler
  2. Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA

    • Zhigang Xie
  3. Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Li-Huei Tsai
  4. Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA

    • Li-Huei Tsai

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Contributions

E.M.P. designed experiments, analysed data and wrote the paper. Z.X. designed and carried out experiments. A.L.N. and M.V. carried out experiments. L-H.T. provided advice and commented on the manuscript. E.M.P., Z.X. and F.B.G. discussed the results and implications and commented on the manuscript at all stages. F.B.G. designed experiments, gave technical support and conceptual advice and revised the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Frank B. Gertler.

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https://doi.org/10.1038/ncb2292

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