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PATTERN FORMATION AND NEURONAL CELL RECOGNITION 
IN THE DROSOPHILA VISUAL SYSTEM 
Hermann Steller, Ph.D., Assistant Investigator 
The overall objective of Dr. Steller's research is to 
understand how functional neuronal circuits are es- 
tablished and maintained during development. He 
and his co-worlcers are currently focusing on three 
major areas. 
Axon Guidance and Neuronal Cell Recognition 
Dr. Steller's group is studying two different stages 
of visual system development to investigate the cel- 
lular and molecular mechanisms by which axons 
find and recognize their proper synaptic partners. 
The Drosophila eye consists of ~800 repeating 
units, called ommatidia. Each ommatidium contains 
eight photoreceptor neurons that represent three 
major cell types projecting to different target cells 
in the optic ganglia. The major class of photorecep- 
tors, Rl-6, sends axons to the first optic ganglion, 
the lamina. Photoreceptor axons from R7 and R8 
project deeper into the brain, to different regions of 
the medulla. The growth cones of these axons must 
navigate over a long distance and make a number of 
highly specific choices. The goal of this research is 
to understand what signals guide axons to their desti- 
nations and how these signals are generated, re- 
ceived, and interpreted. 
Dr. Steller's group has discovered that retinal 
axon fascicles can make at least some of their path- 
finding decisions independently of other fascicles, 
suggesting that they rely on positional guidance 
cues to establish proper retinotopic maps. Position- 
specific differences between photoreceptor cells 
have been revealed by enhancer trap lines that pro- 
duce a gradient of reporter gene expression along 
the dorsoventral axis of the developing retina. The 
gene corresponding to one of these gradient lines 
has been isolated, and mutations in this gene have 
been obtained that result in embryonic lethality. 
The functional and molecular characterization of 
this locus is in progress. 
Dr. Steller and his colleagues have also screened 
for mutations that perturb the projection pattern of 
photoreceptor cells at very early developmental 
stages, when axons enter the brain. A number of mu- 
tants with severely abnormal patterns of axon in- 
growth have been isolated, and the developmental, 
genetic, and molecular characterization of this mate- 
rial has been initiated. 
Dr. Steller's group is also using the optic nerve of 
the Drosophila larva as a simple model system to 
investigate how specific neuronal connections are 
established. They previously identified a gene, dis- 
connected {disco), that is required for establishing 
stable connections between the larval optic nerve 
and its target cells in the developing brain. The 
disco gene has been cloned, and its structure, nu- 
cleotide sequence, and pattern of expression have 
been determined. 
These studies suggest that disco encodes a tran- 
scription factor with autoregulatory properties. 
Consistent with such a function is the group's obser- 
vation that the disco protein has sequence-specific 
DNA-binding activity in vitro and that two high- 
affinity binding sites are located very close to the 
disco transcription unit. Ectopic expression of 
disco protein under an inducible promoter in trans- 
genic flies results in severe developmental defects 
and embryonic lethality. These defects include both 
a drastic reduction of the axon scaffold and connec- 
tivity defects in both the peripheral and central ner- 
vous systems. Experiments are in progress to test the 
idea that disco controls the activity of genes re- 
quired for the establishment of stable connections 
between the larval optic nerve and its target cells. 
(This work was supported by a grant from the Na- 
tional Institutes of Health.) 
Role of Innervation for Neurogenesis and 
Survival of Target Cells 
It has been noticed for many years that synaptic 
input can have a profound influence on the fate and 
differentiation of target cells. In Drosophila, the 
proper development of the adult optic ganglia de- 
NEUROSCIENCE 439 
