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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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