Neuron
Volume 74, Issue 4, 24 May 2012, Pages 676-690
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Article
Optic Chiasm Presentation of Semaphorin6D in the Context of Plexin-A1 and Nr-CAM Promotes Retinal Axon Midline Crossing

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Summary

At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or contralaterally to establish the circuitry for binocular vision. Ipsilateral guidance programs have been characterized, but contralateral guidance programs are not well understood. Here, we identify a tripartite molecular system for contralateral RGC projections: Semaphorin6D (Sema6D) and Nr-CAM are expressed on midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs, but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth promotion. Nr-CAM functions as a receptor for Sema6D. Sema6D, Plexin-A1, and Nr-CAM are all required for efficient RGC decussation at the optic chiasm. These findings suggest a mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1 at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1 receptors on RGCs to implement the contralateral RGC projection.

Highlights

► Plexin-A1 and Nr-CAM are expressed in contralateral RGCs and the optic chiasm midline ► Nr-CAM and Plexin-A1 modulate inhibition by midline Sema6D ► Nr-CAM is a receptor for Sema6D and binds to Plexin-A1 ► Proper RGC axon fasciculation and decussation are dependent on all three factors

Cited by (0)

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Present address: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA

7

Present address: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

8

Present address: Department of Psychiatry, Weill Cornell Medical College, New York, NY 10021, USA

9

Present address: Medical Innovation Center, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan