Extracellular Factors Affecting Neuron Development 
pears to modulate the signals conveyed by inte- 
grin receptor binding to laminin and other pro- 
teins. These signals can be modulated by trophic 
factors, such as NGF. 
In addition to proteins secreted into the extra- 
cellular environment of cells, neurons also recog- 
nize and use for axon extension integral mem- 
brane proteins on the surfaces of different cell 
types. Recent work in our laboratory has identi- 
fied some of the major proteins that neurons use 
for axonal growth in the central and peripheral 
nervous systems. Thus neurons have been shown 
to use both extracellular matrix and cell-cell ad- 
hesion molecules for growth of axons on 
Schwann cells, the major cell type with which 
they interact in peripheral nerves. A similar com- 
bination of adhesive interactions promotes 
growth of retinal axons on astroglia. The move- 
ments of growth cones of retinal ganglion cells 
have been directly monitored in vivo by time- 
lapse microscopy. Injection of antibodies to indi- 
vidual cell adhesion molecules has been shown 
to alter dramatically the behavior of these growth 
cones. 
In studies on interactions of neurons with other 
cells in the brain, it became clear that additional 
adhesion molecules, not yet identified or charac- 
terized, must be important. We have used molec- 
ular biological methods to identify two of these 
with localized expression patterns in the brain. 
One of these, the integrin ag/^n is localized on 
axons in many of the major axon tracts of the 
brain. Its concentration on axons in these tracts 
suggests that it mediates interactions between 
these axons. A potential ligand for this integrin 
that is also localized in these tracts has been iden- 
tified. The second novel adhesion-promoting 
molecule is B-cadherin, a Ca^'^-dependent adhe- 
sion molecule that is also expressed in the ner- 
vous system. It appears to be concentrated in spe- 
cific cells in several areas of the brain. Some but 
not all neurons are able to interact with it. Both 
molecules are also expressed in some areas out- 
side the nervous system. 
Future work will focus on determining how 
these neuronal receptors act to promote growth 
cone motility, how they are regulated during de- 
velopment, and what their importance is in regu- 
lating the grov^T:h of axons during development 
and regeneration. 
356 
