transcriptional control of protein distribution from 
other post-transcriptional mechanisms, the seven- 
less promoter was coupled to the reporter gene, 
lacZ, which encodes (3-galactosidase. Expression of 
P-galactosidase was found to parallel the sevenless 
pattern described previously by Dr. Rubin's group, 
indicating that the cell-specific pattern of sevenless 
^ protein expression in wild-type eye disks is gener- 
ated transcriptionally. This transcription pattern is 
controlled by an enhancer element located in an 
intron of the gene. 
An understanding of the structure and activity of 
the sevenless protein is a prerequisite for under- 
standing the molecular mechanisms of sevenless- 
mediated signaling. Dr. Rubin's group has ex- 
pressed the sevenless protein in Drosophila tissue 
culture cells and studied its synthesis, processing, 
and activity. The sevenless protein possesses pro- 
tein tyrosine kinase activity. The protein is first syn- 
thesized as a 280 kDa glycoprotein precursor that is 
subsequently cleaved into 220 kDa amino-terminal 
and 58 kDa carboxyl-terminal subunits that remain 
associated by noncovalent interactions. The 220 
kDa subunit is glycosylated and contains most of 
the extracellular portion of the protein, whereas 
the 58 kDa subunit is composed of a small portion 
of the extracellular sequences and the intracellular 
protein tyrosine kinase domain. This complex is 
subsequently cleaved into either 49 or 48 kDa car- 
boxyl-terminal fragments, with concomitant degra- 
dation of the rest of the protein. 
The adoption of distinct fates by cells in the de- 
veloping retina that are in such close proximity to 
one another must require precise cell-cell signaling 
mechanisms. This precision must result from the 
specific coincidence in time and space of ligands, 
receptors, and intercellular signal-transducing fac- 
PUBLICATIONS 
tors. In theory the required specificity could 
be achieved by regulation of any combination of 
these proteins. Dr. Rubin's group has begun to 
address this issue by replacing the restricted pat- 
tern of sevenless expression with one where the 
protein is expressed in all cells of the eye disk 
under the control of a heat-shock promoter. Con- 
sistent with a role in receiving a transient inductive 
signal, expression of sevenless was found to be re- 
quired only during a brief period of ommatidial de- 
velopment for formation of the R7 cell. However, 
the complex spatial distribution of sevenless pro- 
tein within the developing ommatidium is not a 
crucial part of the positional information that pro- 
vides specificity to the signal mediated by sevenless, 
suggesting that the necessary specificity is provided 
by the temporal or spatial distribution of its ligand 
or substrate. 
IV Additional Genes Involved in Retinal 
Development. 
Dr. Rubin and his colleagues are using both con- 
ventional mutagenesis and the P element-mediated 
enhancer detector method to carry out extensive 
genetic screens for mutations that affect develop- 
ment of the various cell types in the eye. They have 
isolated and are genetically and phenotypically 
characterizing several new mutations that affect 
ommatidial development. In addition, they are con- 
tinuing their studies of the rough gene. 
Dr. Rubin is also John D. MacArthur Professor of 
Genetics at the University of California at Berkeley 
and Adjunct Professor in the Department of Bio- 
chemistry and Biophysics at the University of Cali- 
fornia School of Medicine at San Francisco. 
Articles 
Baker, N.E., and Rubin, G.M. 1989. Effect on eye development of dominant mutations in Drosophila homo- 
logue of the EGF receptor. Nature 340:150-153. 
Bloomquist, B.T, Shortridge, R.D., Schneuwly S., Perdew, M., Montell, C, Steller, H. , Rubin, G.M. , and Pak, 
WL. 1988. Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in pho- 
totransduction. Ce// 54:723-733. 
Bowtell, D.D.L., Simon, M.A., and Rubin, G.M. 1989. Ommatidia in the developing Drosophila eye require 
and can respond to sevenless for only a restricted period. Cell 56:931-936. 
Kalderon, D., and Rubin, G.M. 1988. Isolation and characterization oi Drosophila cAMP-dependent protein 
kinase genes. Genes Dev 2:1539-1556. 
Kalderon, D., and Rubin, G.M. 1989. cGMP-dependent protein kinase genes in Drosophila. J Biol Chem 
264: 10738-10748^ 
Continued 
530 
