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EXTRACELLULAR FACTORS AFFECTING NEURON DEVELOPMENT 
Louis F. Reichakdt, Ph.D., Investigator 
Dr. Reichardt's laboratory studies soluble and ad- 
hesion-promoting factors that regulate survival and 
differentiation of neurons during development and 
regeneration of the nervous system. 
Development of Axons in the Primary 
Visual Projection 
In past work, laboratory members examined ad- 
hesive interactions promoting axon growth by reti- 
nal neurons over astroglial substrates in vitro, as a 
model to discover interactions likely to be impor- 
tant in vivo for normal development of the retina 
and the retinal tectal projection. These experiments 
suggested that several adhesive receptors on the 
growth cones of the axons of retinal ganglion cells 
promote axon growth. These receptors include 
three cell adhesion molecules — NCAM, N-cadherin, 
and Ll/NgCAM — and several integrin heterodimers. 
During the past year. Dr. David Sretavan has ex- 
tended these studies to the endogenous pathway 
along the neuroepithelium traversed by retinal gan- 
glion cell axons. To label these axons, the embry- 
onic eye has been injected with lipophilic fluores- 
cent dyes that are incorporated into retinal ganglion 
cell membranes. With these dyes, fluorescence 
imaging has been used to monitor movements of in- 
dividual growth cones in the optic stalk, the portion 
of the visual pathway between the retina and optic 
chiasm. The early growth cones in this pathway ex- 
hibit regular movements toward the future optic 
chiasm. Individual growth cones move over the neu- 
roepithelial substrate and at early times are not ex- 
tensively fasciculated with each other. Injection of 
antibodies to LI inhibits their movements, indicat- 
ing that at least one of the adhesion-promoting mole- 
cules important in vitro is also important in vivo. 
The behavior of these growth cones has also been 
examined in the optic chiasm, a major choice point 
in the visual projection. From there each growth 
cone projects either contralaterally or ipsilaterally, 
depending primarily on the position of its cell body 
in the retina. In the developing optic chiasm, 
growth cones contact each other intermittently, but 
primarily grow in contact with the neuroepithelial 
cell substrate. Numerous examples of contra- and 
ipsilaterally projecting growth cones have been visu- 
alized. When ipsilaterally projecting growth cones 
turn, they reorient within 10-20 minutes. These de- 
cisions always appear to occur in the chiasm, and 
observation suggests that they depend on local in- 
formation present in the chiasm. 
Dr. Sretavan has identified a population of early- 
developing neurons that are candidates to regulate 
the growth of retinal ganglion cell growth cones in 
the chiasm and in more-distal regions of the visual 
projection. These neurons are localized in the vicin- 
ity of the future optic chiasm and project to the dor- 
sal surface of the embryonic midbrain, the approxi- 
mate region innervated by retinal ganglion cells, at 
times in development preceding the arrival of reti- 
nal ganglion cell growth cones at the optic chiasm. 
In double-labeling experiments, growth cones from 
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