Development of the Drosophila Visual System 
Gerald M. Rubin, Ph.D. — Investigator 
Dr. Rubin is also John D. MacArthur Professor of Genetics at the University of California, Berkeley, and 
Adjunct Professor of Biochemistry and Biophysics at the University of California, San Francisco, School 
of Medicine. He received his B.S. degree in biology from the Massachusetts Institute of Technology and his 
Ph.D. degree in molecular biology from the University of Cambridge. Dr. Rubin's postdoctoral work was 
done at Stanford University with David Hogness. He has held faculty positions at Harvard Medical School 
and the Carnegie Institution of Washington. Dr. Rubin is a member of the National Academy of Sciences 
and counts among his other honors the American Chemical Society Eli lilly Award in Biological Chemistry. 
RESEARCH in our laboratory is directed to- 
ward studies of differentiation and gene regu- 
lation in the developing nervous system. Our ex- 
perimental approach involves studying genes 
whose mutations disrupt neural development. 
During the past year, we have focused our work 
on several genes important for the determination 
of cell fates in the developing retina of the fruit 
fly Drosophila. 
Two very different but not exclusive mecha- 
nisms can account for the selection of distinct 
developmental pathways. First, cells may be pro- 
grammed in a lineage-dependent manner by the 
asymmetric partitioning of determinants during 
cell division. Different developmental pathways 
are then selected in the daughter cells in re- 
sponse to the different localized determinants. Al- 
ternatively, cellular differentiation may occur in 
a lineage-independent manner, where the posi- 
tion that a cell occupies in a developing field 
determines its fate. In this case, diffusible sub- 
stances, such as hormones, or interactions with 
adjacent cells are the primary determinants of 
cellular differentiation. Although the mecha- 
nisms used to read and interpret such positional 
information are largely unknown, short-range 
cellular interactions are thought to be of princi- 
pal importance in a wide variety of developmen- 
tal phenomena. 
The compound eye of Drosophila melanogas- 
ter is an attractive system to study the mecha- 
nisms underlying lineage-independent develop- 
mental decisions, since it consists of a small 
number of different cell types that develop in a 
lineage-independent manner. The compound eye 
is a two-dimensional array of 800 repeating units, 
or ommatidia. Each ommatidium contains 8 pho- 
toreceptor cells as well as 1 2 nonneuronal acces- 
sory cells. Each photoreceptor cell has a distinct 
cellular identity, based on both its position 
within the ommatidium and its projection pattern 
to the optic lobes of the brain. The stereotyped 
arrangement of this small number of nerve cells, 
together with the dispensability of the visual sys- 
tem under laboratory conditions, makes the com- 
pound eye an attractive model system to study 
genes involved in the specification of nerve cells. 
Assembly of ommatidia begins in an initially 
unpatterned monolayer of epithelial cells, the 
eye imaginal disc. Ommatidial assembly does not 
occur synchronously throughout the disc but in- 
stead begins at the posterior edge and progresses 
anteriorly. Eye discs removed from larvae just 
prior to pupariation show a smoothly graded se- 
ries of ommatidia at different stages of develop- 
ment, covering just over half of the disc. Examina- 
tion of individual cells in the forming ommatidia 
has shown that the photoreceptors differentiate 
in a fixed sequence, beginning with the central 
R8 photoreceptor and proceeding pairwise with 
R2 and R5, R3 and R4, Rl and R6, and finally R7. 
The fate of a cell within a developing ommatid- 
ium appears to be governed by the specific com- 
bination of signals received by that cell from its 
immediate neighbors. We would like to under- 
stand how such signals are generated, received, 
and interpreted. Our approach has been to study 
mutations that specifically disrupt these pro- 
cesses, as illustrated by our studies of the seven- 
less gene. 
The sevenless gene is essential for the develop- 
ment of a single type of photoreceptor cell. In the 
absence of proper sevenless function, the cells 
that would normally become the R7 photorecep- 
tors become instead nonneuronal cells. Previous 
morphological and genetic analysis has indicated 
that the product of the sevenless gene is involved 
in reading or interpreting the positional informa- 
tion that specifies this particular developmental 
pathway. We have isolated and characterized the 
sevenless gene. Our data indicate that sevenless 
encodes a transmembrane protein with a tyrosine 
kinase domain. The structural analogies between 
the sevenless protein and certain hormone recep- 
tors suggest that developmental pathway selec- 
tions dependent on cell-cell interactions may 
involve molecular mechanisms similar to physio- 
logical or developmental changes induced by 
long-range diffusible factors. 
To investigate the role of the sevenless protein 
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