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Semaphorin 3A is a chemoattractant for cortical apical dendrites

Abstract

The apical dendrites of pyramidal neurons integrate inputs from various cortical layers and are central to information processing. Here we show that the growth of apical dendrites towards the pial surface is regulated by a diffusible chemoattractant present at high levels near the marginal zone. A major component of this signal is semaphorin 3A (Sema3A), which was previously characterized as a chemorepellant for cortical axons. Soluble guanylate cyclase is asymmetrically localized to the developing apical dendrite, and is required for the chemoattractive effect of Sema3A. Thus the asymmetric localization of soluble guanylate cyclase confers distinct Sema3A responses to axons and dendrites. These observations reveal a mechanism by which a single chemotropic signal can pattern both axons and dendrites during development.

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Figure 1: An extracellular signal present in the cerebral wall directs apical dendrite outgrowth towards the marginal zone.
Figure 2: Apical dendrites are attracted by a diffusible signal near the marginal zone.
Figure 3: Sema3A is necessary and sufficient for appropriate apical dendrite orientation.
Figure 4: The Sema3A receptor Neuropilin-1 is present on apical dendrites, and is required for correct apical dendrite orientation.
Figure 5: Soluble guanylate cyclase is asymmetrically localized to the apical dendrite in developing pyramidal neurons.
Figure 6: Inhibition of soluble guanylate cyclase and protein kinase G disrupts apical dendrite orientation.

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Acknowledgements

We thank A. Kolodkin and D. Ginty for the AP-Sema3A plasmid and the anti-Neuropilin-1 antibody, R. Giger for sharing data on SEMA3A expression in the cortex, M. Okabe for the GFP-expressing mice, O. Behar and M. Fishman for SEMA3A heterozygous mice, members of the Ghosh lab for discussions, and A. Kolodkin, D. Ginty, R. Giger and M. Tessier-Lavigne for comments on the manuscript. This work was supported by the NIH (A.G.) and the Pew Scholars Program (A.G.).

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Polleux, F., Morrow, T. & Ghosh, A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 404, 567–573 (2000). https://doi.org/10.1038/35007001

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