Extracellular Factors Affecting Neuron Development 
hibiting changes in the activity of integrin recep- 
tors on their surfaces. These changes occur rap- 
idly and can be modulated by external and 
internal agents. Yet a third level of regulation ap- 
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 nerve growth factor. 
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 on central and peripheral cells. 
Thus neurons have been shown to use both extra- 
cellular matrix and cell-cell adhesion molecules 
for growth of axons on Schwann cells, the major 
cell type with which they interact in peripheral 
nerves. The cell adhesion molecules include 
members of the immunoglobulin superfamily 
and members of a new family of calcium-depen- 
dent adhesion molecules, the cadherins. 
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 a^^^, 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. The second novel adhesion-promot- 
ing molecule is B-cadherin, a Ca^^-dependent ad- 
hesion molecule that is also expressed in the ner- 
vous system. It appears to be concentrated in 
specific cells in several areas of the brain. 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 growth of axons during development 
and regeneration. 
368 
