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The Journal of Neuroscience, September 29, 2004, 24(39):8428-8435; doi:10.1523/JNEUROSCI.2349-04.2004

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Development/Plasticity/Repair
Repulsion and Attraction of Axons by Semaphorin3D Are Mediated by Different Neuropilins In Vivo

Marc A. Wolman,^1,2 Yan Liu,¹ Hiroshi Tawarayama,³ Wataru Shoji,³ and Mary C. Halloran^1,2

¹Departments of Zoology and Anatomy and ²Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, and ³Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan

Class 3 semaphorins are known to repel and/or sometimes attract axons; however, their role in guiding developing axons in the CNS in vivo is still essentially unknown. We investigated the role of Semaphorin3D (Sema3D) in the formation of the early axon pathways in the zebrafish CNS. Morpholino knock-down shows that Sema3D is essential for the correct formation of two early axon pathways. Sema3D appears to guide axons of the nucleus of the medial longitudinal fasciculus (nucMLF) by repulsion and modulation of fasciculation. In contrast, Sema3D appears to be attractive to telencephalic neurons that form the anterior commissure (AC). Knock-down of Neuropilin-1A (Npn-1A) phenocopied the effects of Sema3D knock-down on the nucMLF axons, and knock-down of either Npn-1A or Npn-2B phenocopied the defects of the AC. Furthermore, simultaneous partial knock-down experiments demonstrated genetic interactions among Sema3D, Npn-1A, and Npn-2B. Together, these data support the hypothesis that Sema3D may act as a repellent through receptors containing Npn-1A and as an attractant via receptors containing Npn-1A and Npn-2B.

Key words: semaphorin; neuropilin; axon guidance; fasciculation; chemoattraction; chemorepulsion

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Received June 15, 2004; revised August 16, 2004; accepted August 16, 2004.

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