Control of Cell Fate During Vertebrate Neuronal Development 
neuron by its presynaptic partner may endow it 
with the machinery to respond to key survival 
factors secreted by its postsynaptic target. In this 
way, the estabHshment of functional connections 
between a neuron, its input, and its output target 
could be coordinated. 
Control of Neuron-Specific Gene Expression 
As it differentiates, the chromaffin-neuron pre- 
cursor expresses genes that are not expressed in 
other cell types. How such specific expression is 
achieved is a basic question in modern develop- 
mental biology. Studies in blood and lymphoid 
cells have revealed that genes such as that encod- 
ing hemoglobin are specifically turned on in the 
appropriate cells by activator proteins, present 
only in those cells. We have studied a neuron- 
specific gene, SCGIO, and found that a different 
mechanism restricts its expression to developing 
neurons. SCO 1 0 appears to be specifically turned 
off in all tissues except neurons; this repression is 
somehow relieved in neurons and not in other 
cells. We have made advances in identifying a 
protein involved in the repression of SCGIO. This 
"silencer" protein is present in nonneuronal 
cells and tissues but not in neuronal cells, consis- 
tent with the idea that it shuts off SCGIO every- 
where except in the nervous system. This same 
silencer protein also appears to be involved in 
shutting off other neuron-specific genes. This 
suggests that specific de-repression may be a 
common mechanism for controlling the expres- 
sion of neuron-specific genes and that a common 
repressor protein may silence the expression of 
several such genes. Future efforts will be directed 
at cloning the gene for this repressor protein and 
understanding how it in turn is controlled. 
Neural Development in Mammals 
and Drosophila Uses Similar 
Regulatory Molecules 
We have used the chromaffin-neuron precursor 
cell lines to isolate new genes that may be candi- 
dates for controlling the development of these 
cells. Our approach is based on the idea that Dro- 
sophila genes controlling neural development 
might also be conserved in mammals. One impor- 
tant set of genes that control neuronal develop- 
ment in Drosophila are those of the achaete- 
scute complex (AS-C) . These scute genes encode 
a group of related proteins that act by binding to 
DNA, thereby controlling the activity of other 
genes. We succeeded in isolating two scute- 
related genes from the rat chromaffin-neuron 
precursor cell line. The structures of these genes 
are remarkably similar to those of their fruit fly 
counterpans. Moreover, the rat scute-veliAed 
genes appear to be expressed specifically in neu- 
ronal precursor cells, like their counterparts in 
the fly. These data indicate that there has been a 
striking parallel conservation of gene structure 
and cell type specificity during evolution. They 
further suggest that the scwfe-related genes may 
control the development of mammalian neurons. 
These exciting findings suggest that the molecu- 
lar mechanisms controlling nerve cell develop- 
ment in vertebrate and invertebrate organisms 
may be fundamentally similar. We are now in the 
process of testing this hypothesis by making tar- 
geted mutations in these genes in mice. 
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