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DETERMINATION OF NEURONAL CELL FATES IN THE DEVELOPING FLY 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. The current work focuses 
on the development of the visual system, and in par- 
ticular, on understanding the signal transduction 
pathways that lead to the determination of cell fates. 
The developing Drosophila retina has proved to 
be well suited for genetic, molecular, and cellular 
experiments aimed at understanding the mecha- 
nisms of signal transduction. The adult eye is made 
up of a simple array of ~800 20-cell units called 
ommatidia. Each ommatidium contains eight pho- 
toreceptor cells, R1-R8, as well as four lens- 
secreting cone cells and eight other accessory cells. 
The cells that make up each ommatidium are 
thought to be recruited by a series of local cell-cell 
interactions, with differentiating cells instructing 
their immediate neighbors to adopt panicular fates. 
The R7 photoreceptor is the last of the eight pho- 
toreceptors to be recruited to the developing om- 
matidium. The presumptive R7 cell appears to face 
a simple choice between two alternative cell fates: it 
will develop into an R7 photoreceptor if it receives 
a signal that is initiated by activation of the Sevenless 
protein-tyrosine kinase receptor; otherwise it will 
adopt a nonneuronal cone cell fate. During the past 
year. Dr. Rubin's group has made significant prog- 
ress in understanding the inductive event that leads 
to the recruitment of the R7 photoreceptor by using 
genetic analysis to reveal aspects of the intracellular 
pathway that transduces the signal initiated by acti- 
vation of the Sevenless receptor. Two features make 
the Sevenless pathway ideal for genetic approaches 
to understanding signaling by receptor tyrosine ki- 
nases. First, both the R7 cell and the Sevenless pro- 
tein are dispensable for viability and fertility. Sec- 
ond, the functioning of this signaling pathway can 
be inferred from the presence of the R7 cell in a live, 
anesthetized fly. 
Transmembrane tyrosine receptors play impor- 
tant roles in a variety of physiological and develop- 
mental processes. How the signals initiated by acti- 
vation of such receptors effect changes in cell 
physiology are still poorly understood. The intracel- 
lular machinery used to interpret and implement 
the instruction (s) conveyed by the activation of tyro- 
sine kinase receptors is being actively investigated 
in a wide variety of developing organisms and tis- 
sues using both genetic and biochemical ap- 
proaches. Biochemical studies with mammalian 
protein-tyrosine kinase receptors have led to the 
identification of proteins that bind to or are phos- 
phorylated by tyrosine kinases. Although some of 
these interactions suggest potential mechanisms 
of signal transmission, their role in vivo is still 
unclear. 
Sensitizing the System — A Way to Identify 
Particular Roles of Widely Utilized Proteins 
Given the widespread role of tyrosine kinases in 
development, it is likely that the vast majority of 
genes whose products act in the Sevenless-mediated 
signal transduction pathway would also act in ear- 
NEUROSCIENCE 429 
