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We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing optic chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the optic chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and optic chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse optic chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina.

Original publication

DOI

10.1002/jnr.21717

Type

Journal article

Journal

J Neurosci Res

Publication Date

09/2008

Volume

86

Pages

2581 - 2590

Keywords

Animals, Axons, Coculture Techniques, Female, Functional Laterality, Growth Inhibitors, Membrane Proteins, Mice, Mice, Inbred C57BL, Myelin Proteins, Nogo Proteins, Optic Chiasm, Organ Culture Techniques, Visual Pathways