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Semaphorin 3A is a chemoattractant for cortical apical dendrites


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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  1. Miller,M. W. in Cerebral Cortex (eds Peters, A. & Jones, E. G.) 133– 175 (Plenum, New York, London, 1988).

    Book  Google Scholar 

  2. Gilbert,C. D. Microcircuitry of the visual cortex. Annu. Rev. Neurosci. 6, 217–247 (1983).

    Article  CAS  PubMed  Google Scholar 

  3. Larkum,M. E., Zhu,J. J. & Sakmann,B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Fishell,G. Striatal precursors adopt cortical identities in response to local cues. Development 121, 803–812 (1995).

    CAS  PubMed  Google Scholar 

  5. McAllister,A. K., Lo,D. C. & Katz,L. C. Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 15, 791– 803 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Wu,G. & Cline,H. Stabilization of dendritic arbor structure in vivo by CaMKII. Science 279, 222– 226 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Tessier-Lavigne,M. & Goodman,C. S. The molecular biology of axon guidance. Science 274, 1123 –1133 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Kolodkin,A. L. Semaphorin-mediated neuronal growth cone guidance. Prog. Brain Res. 117, 115–132 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  9. Polleux,F., Giger,R. J., Ginty,D. D., Kolodkin,A. L. & Ghosh, A. Patterning of cortical efferent projections by semaphorin-neuropilin interactions. Science 282, 1904– 1906 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Okabe,M., Ikawa,M., Kominami,K., Nakanishi,T. & Nishimune, Y. ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett. 407, 313– 319 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Kolodkin,A. L. et al. Neuropilin is a semaphorin III receptor. Cell 90, 753–762 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Catalano,S. M., Messersmith,E. K., Goodman, C. S., Shatz,C. J. & Chédotal,A. Many major CNS axon projections develop normally in the absence of semaphorin III. Mol. Cell. Neurosci. 11, 173–182 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  13. Chédotal,A. et al. Semaphorins III and IV repel hippocampal axons via two distinct receptors. Development 125, 4313– 4323 (1998).

    PubMed  Google Scholar 

  14. Skaliora,I., Singer,W., Betz,H. & Puschel,A. W. Differential patterns of semaphorin expression in the developing rat brain. Eur. J. Neurosci. 10, 1215–1229 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. He,Z. & Tessier–Lavigne,M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90, 739–751 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Behar,O., Golden,J. A., Mashimo,H., Schoen,F. J. & Fishman, M. C. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature 383, 525–528 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Song,H.-J. et al. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 1515–1518 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Garthwaite,J. et al. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol. Pharmacol. 48, 184–188 (1995).

    CAS  PubMed  Google Scholar 

  19. Butt,E., Eigenthaler,M. & Genieser, H. G. (Rp)-8-pCPT-cGMPS, a novel cGMP-dependent protein kinase inhibitor. Eur. J. Pharmacol. 269, 265–268 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Harris,D. N., Asaad,M. M., Phillips,M. B., Goldenberg,H. J. & Antonaccio,M. J. Inhibition of adenylate cyclase in human blood platelets by 9-substituted adenine derivatives. J. Cyclic Nucleotide Res. 5, 125–134 (1979).

    CAS  PubMed  Google Scholar 

  21. Giger,R. J., Wolfer,D. P., De Wit,G. M. & Verhaagen,J. Anatomy of rat semaphorin III/collapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis. J. Comp. Neurol. 375, 378–392 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  22. Bagnard,D., Lohrum,M., Uziel,D., Puschel,A. W. & Bolz, J. Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections. Development 125, 5043–5053 ( 1998).

    CAS  PubMed  Google Scholar 

  23. Parent,C. A., Blacklock,B. J., Froehlich, W. M., Murphy,D. B. & Devreotes,P. N. G protein signaling events are activated at the leading edge of chemotactic cells. Cell 95, 81–91 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. Parent,C. A. & Devreotes,P. N. A cell's sense of direction. Science 284, 765–770 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Baas,P. W. Microtubules and neuronal polarity: lessons from mitosis. Neuron 22, 23–31 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  26. Robinson,K. R. & Miller,B. J. The coupling of cyclic GMP and photopolarization of Pelvetia zygotes. Dev. Biol. 187, 125–130 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  27. Hong,K. et al. A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97, 927– 941 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Bashaw,G. J. & Goodman,C. S. Chimeric axon guidance receptors: the cytoplasmic domains of slit and netrin receptors specify attraction versus repulsion. Cell 97, 917– 926 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Giger,R. J. et al. Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor fucntion and specificity. Neuron 21, 1079–1092 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  30. Flanagan,J. G. & Leder,P. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell 63, 185–194 ( 1990).

    Article  CAS  PubMed  Google Scholar 

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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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Correspondence to Anirvan Ghosh.

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Polleux, F., Morrow, T. & Ghosh, A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 404, 567–573 (2000).

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