DEVELOPMENT OF THE DROSOPHILA EYE 
Gerald M. Rubin, Ph.D., Investigator 
Dr. Rubin's laboratory studies various aspects of 
gene expression and differentiation in Drosophila, 
with emphasis on molecular and genetic ap- 
proaches to neurobiology. Their current work is fo- 
cused on the development of the visual system. 
I. Development of Drosophila Retina. 
The compound eye of Drosophila is a two- 
dimensional array of 800 repeating units, or om- 
matidia. Each ommatidium contains eight photo- 
receptor cells (R1-R8), as well as pigment cells, 
lens-secreting cells, and a mechanosensory bristle. 
Each photoreceptor cell has a distinct cellular iden- 
tity, based on 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 dispensa- 
bility of the visual system under laboratory condi- 
tions, makes the compound eye an attractive model 
system to study genes involved in the specification 
of nerve cells. 
The development of the compound eye of Dro- 
sophila requires the formation of a precise pattern 
of differentiated cell types. The formation of this 
pattern begins in the eye imaginal disk of third in- 
star larvae, where cells are progressively recruited 
from an unpatterned epithelium to form the indi- 
vidual units, or ommatidia, of the eye. Examination 
of individual cells in the forming ommatidia has 
shown that the photoreceptors differentiate in a 
fixed sequence, beginning with the central R8 pho- 
toreceptor and proceeding pairwise with R2 and 
R5, R3 and R4, Rl and R6, and finally R7. The re- 
cruitment and differentiation of these cells occurs 
in response to positional cues, generated, sensed, 
and responded to by cells in the developing field. 
Components of these signaling pathways can, in 
principle, be identified by isolating mutant flies in 
which the developmental process is interrupted at 
specific stages. 
II. Ellipse and scabrous Genes: Spacing the 
R8 Cells. 
An early step in the formation of ommatidia is the 
distribution of cells that will give rise to the R8 
cells. Dr. Rubin's group is studying two mutations, 
scabrous and Ellipse (Elp), that affect this process 
in opposite ways. In scabrous mutants it appears 
that too many cells begin to differentiate as R8 
cells, whereas in the mutant Elp, very few cells do. 
The scabrous gene has been cloned, and its struc- 
ture and expression are being analyzed. From ge- 
netic studies. Dr. Rubin and his colleagues have 
demonstrated that Elp is a dominant mutation in 
the gene that encodes the Drosophila homologue 
of the mammalian epidermal growth factor recep- 
tor (DER) . How ommatidia come to form in a regu- 
lar spatial array is unknown, but local competition 
and lateral inhibition between disk cells may be in- 
volved. It is not known why Elp mutations predom- 
inantly affect the eye, when amorphic mutations 
are lethal to the embryo. Possibly the increased 
DER activity in Elp is specific to the developing eye, 
or the eye may be especially sensitive to such an in- 
crease. It is also not known whether Elp mutations 
increase the expression of DER protein or enhance 
its activity, perhaps with respect to an eye-specific 
ligand or target. 
III. The sevenless Gene. 
The best-characterized mutant affecting retinal 
development is sevenless. The sevenless gene is es- 
sential for the development of a single type of pho- 
toreceptor cell; in the absence of proper sevenless 
function the cells that would normally become the 
R7 photoreceptors become nonneuronal, lens- 
secreting cells. Previous morphological and genetic 
analyses have indicated that the product of the 
sevenless gene is involved in reading or interpreting 
the positional information that specifies this partic- 
ular developmental pathway. 
In previous reports Dr. Rubin's group described 
the isolation, nucleotide sequence, and expression 
pattern of the sevenless gene. The sevenless gene 
encodes a protein tyrosine kinase cell surface re- 
ceptor that is expressed in a highly specific and 
complex pattern in the developing Drosophila eye. 
Changes in expression of the sevenless protein 
occur very rapidly; substantial differences in pro- 
tein expression can be observed between neighbor- 
ing ommatidia that are only ~2 h apart in the de- 
velopmental sequence. The sevenless protein is the 
only example of a tyrosine kinase receptor in which 
such a dynamic pattern of expression in a develop- 
ing tissue has been described. It was therefore of 
interest to establish the mechanism by which this 
cell-specific pattern is generated. To distinguish 
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