Development of the Drosophila Visual System 
ing sevenless protein, we have shown that there 
is only a brief period during eye development 
when the sevenless protein is required for the 
formation of the R7 photoreceptor. Our results 
are consistent with the proposal that sevenless 
directly reads positional information required to 
specify the R7 developmental pathway. 
A major current goal is to determine how acti- 
vation of the sevenless tyrosine kinase instructs a 
ceil to become an R7 photoreceptor. Defining 
the biologically relevant substrates of tyrosine ki- 
nase receptors has been a long-standing and diffi- 
cult problem. We have used two strategies in a 
genetic approach toward the identification of 
genes whose products act downstream of seven- 
less, including those that might be direct sub- 
strates for the sevenless kinase. 
First, we have looked for other mutations that 
give the same phenotype as sevenless — transfor- 
mation of the R7 cell into a nonneuronal cell 
type. In this way we isolated the seven in-absen- 
tia {sina) gene. Function of sina is required only 
in R7 for correct R7 cell development. The sina 
protein, which has a potential metal-binding do- 
main, is localized in the nuclei of several omma- 
tidial precursor cells, including R7, and sina ex- 
pression in R7 appears before R7 overtly begins 
to differentiate. These data indicate that the sina 
gene product is necessary at a stage in the deter- 
mination of R7 cell fate when R7 receives and 
interprets developmental signals from neighbor- 
ing cells, and possibly acts by regulating gene 
expression. 
Second, we utilized a crippled sevenless pro- 
tein, whose activity is just barely adequate to 
specify R7 cell development, to establish a highly 
sensitive assay for other components of this signal 
transduction pathway. Using this assay we looked 
for other genes in which a 50 percent reduction 
of the level of their protein products resulted in a 
failure to specify R7 cells. In this way we have 
identified seven genes that appear to encode 
products that act to interpret the signal mediated 
by the sevenless receptor. 
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