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Semaphorin-3A guides radial migration of cortical neurons during development

Nature Neuroscience volume 11, pages 36–44 (2008)Cite this article

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Abstract

Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure. Here we report that the radial migration of rat layer II/III cortical neurons requires guidance by the extracellular diffusible factor Semaphorin-3A (Sema3A). This factor is expressed in a descending gradient across the cortical layers, whereas its receptor neuropilin-1 (NP1) is highly expressed in migrating neurons. Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes their radial migration by disrupting their radial orientation during migration without altering their cell fate. Studies in cultured cortical slices further show that the endogenous gradient of Sema3A is required for the proper migration of newborn neurons. In addition, transwell chemotaxis assays show that isolated newborn neurons are attracted by Sema3A. Thus, Sema3A may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers.

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Figure 1: Downregulating NP1 impairs the radial migration of cortical neurons in vivo.
Figure 2: Impaired radial migration in the conditional downregulation of NP1 in mice.
Figure 3: Effect of downregulation of NP co-receptors on radial migration.
Figure 4: Effect of NP1 RNAi on the morphology of cortical neurons.
Figure 5: Disruption of Sema3A to NP1 signaling impedes radial migration in cultured cortical slices.
Figure 6: Disruption of Sema3A-NP1 signaling impedes radial migration in living cortical slices.
Figure 7: Sema3A has an attractive role in cortical radial migration.

Change history

  • 09 December 2007

    In the version of the supplementary information originally published online for this manuscript, the legends for Supplementary Video #3 and Supplementary Video #4 were inadvertently switched. This error has now been corrected and the legends correctly describe the appropriate videos

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Acknowledgements

We thank M.-m. Poo for discussion and comments on the manuscript, A. Kolodkin and D. Ginty for providing the NP1-floxed mouse line, Q. Hu for technical support in confocal microscopy, J.-Y. Yu for cell culture, and Y. Wang for electroporation experiments. This work was supported by 973 projects (2006CB806600, 2006CB943903) and grants from the National Natural Science Foundation of China (30300103, 30721004) and the Shanghai government (06QH14017).

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Author notes

  1. Gang Chen, Jian Sima and Ming Jin: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuroscience and Key State Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, 320 Yue Yang Road, Shanghai, 200031, China

    Gang Chen, Jian Sima, Ming Jin, Kai-yu Wang, Xiao-jing Xue, Wang Zheng, Yu-qiang Ding & Xiao-bing Yuan

  2. Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China

    Gang Chen, Jian Sima, Kai-yu Wang, Xiao-jing Xue & Wang Zheng

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  1. Gang Chen
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Contributions

G.C. conducted most of the in vivo and in vitro experiments, J.S. prepared all constructs and carried out the in situ hybridization experiments, M.J. conducted the immunohistochemistry and biochemistry experiments and the data analysis, K.-y.W. contributed to data analysis and genotyping, X.-j.X. and W.Z. contributed to part of the in vivo experiments, Y.-q.D. contributed to setting up the experimental techniques, and X.-b.Y. supervised the project and wrote the manuscript.

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Correspondence to Xiao-bing Yuan.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Tables 1–6 and Methods (PDF 2549 kb)

Supplementary Video 1

Cultured slices were obtained fro sections of P1 rat brains electroporated at E16 with EYFP. Images showed the migration of EYFP-labeled neurons during the 3-h live imaging with the interval of 15 min. Scale bar, 20 μm. (MOV 1579 kb)

Supplementary Video 2

Cultured slices were obtained from sections of P1 rat brains electroporated at E16 with EYFP and incubated with anti-NP1 antibody (10 μg ml−1) for 4 h. Images showed the migration of EYFP-labeled neurons during the following 3-h live imaging with the interval of 15 min. Scale bar, 20 μm. (MOV 1476 kb)

Supplementary Video 3

Cultured slices were obtained from sections of P1 rat brains electroporated at E16 with EYFP plus NP1-RNAi1. Images showed the migration of EYFP-labeled neurons during the 3-h live imaging with the interval of 15 min. Scale bar, 20 μm. (MOV 1748 kb)

Supplementary Video 4

Cultured slices were obtained from sections of P1 rat brains electroporated at E16 with EYFP and incubated with Sema3A (1 μg ml−1) for 4 h. Images showed the migration of EYFP-labeled neurons during the following 3-h live imaging with the interval of 15 min. Scale bar, 20 μm. (MOV 1648 kb)

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Chen, G., Sima, J., Jin, M. et al. Semaphorin-3A guides radial migration of cortical neurons during development. Nat Neurosci 11, 36–44 (2008). https://doi.org/10.1038/nn2018

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