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The Journal of Neuroscience, July 1, 2000, 20(13):4983-4991

Slit Inhibition of Retinal Axon Growth and Its Role in Retinal Axon Pathfinding and Innervation Patterns in the Diencephalon

Thomas Ringstedt1, Janet E. Braisted1, Katja Brose2, Thomas Kidd3, Corey Goodman3, Marc Tessier-Lavigne2, and Dennis D. M. O'Leary1

1 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, 2 Departments of Anatomy, and Biochemistry and Biophysics, University of California, San Francisco, California 94143-0452, and 3 Department of Molecular and Cell Biology, University of California, Berkeley, California 94720

We have analyzed the role of the Slit family of repellent axon guidance molecules in the patterning of the axonal projections of retinal ganglion cells (RGCs) within the embryonic rat diencephalon and whether the slits can account for a repellent activity for retinal axons released by hypothalamus and epithalamus. At the time RGC axons extend over the diencephalon, slit1 and slit2 are expressed in hypothalamus and epithalamus but not in the lateral part of dorsal thalamus, a retinal target. slit3 expression is low or undetectable. The Slit receptors robo2, and to a limited extent robo1, are expressed in the RGC layer, as are slit1 and slit2. In collagen gels, axon outgrowth from rat retinal explants is biased away from slit2-transfected 293T cells, and the number and length of axons are decreased on the explant side facing the cells. In addition, in the presence of Slit2, overall axon outgrowth is decreased, and bundles of retinal axons are more tightly fasciculated. This action of Slit2 as a growth inhibitor of retinal axons and the expression patterns of slit1 and slit2 correlate with the fasciculation and innervation patterns of RGC axons within the diencephalon and implicate the Slits as components of the axon repellent activity associated with the hypothalamus and epithalamus. Our findings suggest that in vivo the Slits control RGC axon pathfinding and targeting within the diencephalon by regulating their fasciculation, preventing them or their branches from invading nontarget tissues, and steering them toward their most distal target, the superior colliculus.

Key words: axon guidance; axon fasciculation; axon repellents; chemorepellents; robo1; robo2; hypothalamus; retinal ganglion cells


Copyright © 2000 Society for Neuroscience  0270-6474/00/20134983-09$05.00/0


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