Pattern Formation and Neuronal Cell Recognition 
in the Drosophila Visual System 
Hermann Steller, Ph.D. — Assistant Investigator 
Dr. Steller is also Assistant Professor of Neurobiology at the Massachusetts Institute of Technology and 
Adjunct Assistant Neurobiologist at the Massachusetts General Hospital. He was born in the Federal Re- 
public of Germany and received a Diplom in biology from the Johann- Wolf gang- Goethe University, 
Frankfurt. His graduate studies were done with Vincenzo Pirrotta at the European Molecular Biology 
laboratory and with Ekkehard Bautz at Ruprechts-Karls University in Heidelberg. His postdoctoral work 
was done with Gerald Rubin in the Department of Biochemistry at the University of California, Berkeley. 
Dr. Steller is currently also a Searle Scholar and a Pew Fellow in the Biomedical Sciences. 
THE overall goal of our research is to under- 
stand how the enormous diversity and speci- 
ficity of individual neurons arise during develop- 
ment and how these neurons establish highly 
specific patterns of interconnections. We address 
these questions primarily by exploring the Dro- 
sophila visual system, where it is possible to ap- 
ply powerful genetic and molecular techniques 
to study the development of individual cell types. 
We have identified mutations that affect the pro- 
jection pattern of specific axons, the production 
of neurons from neuronal precursor cells, and the 
pattern of cell death, and have begun to character- 
ize several of these at the cellular and molecular 
level. We hope that our results will eventually 
contribute to a better understanding of human 
neurological disorders. 
Axon Guidance and Neuronal Cell 
Recognition 
We are studying two diff'erent stages of visual 
system development to investigate the cellular 
and molecular mechanisms by which axons find 
and recognize their proper synaptic partners. The 
optic nerve of the Drosophila larva is a simple, 
well-described model system. Connectivity de- 
fects of the larval optic nerve can be rapidly and 
reliably detected in mutant embryos by staining 
with neuron-specific antibodies. In addition, a 
simple behavioral test, larval phototaxis, pro- 
vides an assay for functional connections of the 
larval optic nerve. This has allowed us to screen 
systematically for mutants with abnormal axonal 
projections, which can be subsequently analyzed 
in detail with respect to defects in axonal guid- 
ance, target recognition, and synapse formation. 
We have identified a small number of loci that 
are required for the establishment of stable con- 
nections between the larval optic nerve and its 
target cells in the developing embryonic brain. 
One of the corresponding genes, disconnected 
{disco), has been analyzed at the molecular level 
and appears to encode a transcription factor. We 
are currently testing the idea that disco regulates 
the expression of cell adhesion and/or cell recog- 
nition molecules that are required for the estab- 
lishment of stable connections between the larval 
optic nerve and its target cells in the brain. 
More recently we have begun to study axon 
guidance and neuronal cell recognition in the 
adult visual system. The compound eye of Dro- 
sophila consists of approximately 800 repeating 
units called ommatidia. Each ommatidium con- 
tains eight photoreceptor neurons, which repre- 
sent three major cell types that project to differ- 
ent target cells in the optic ganglia. The major 
class of photoreceptors, Rl-6, establishes synap- 
tic connections with neurons in the first optic 
ganglion, the lamina. Photoreceptor axons from 
R7 and R8 project deeper into the brain to differ- 
ent regions of the second ganglion, the medulla. 
Early during visual system development, all eight 
photoreceptor axons from each ommatidium 
grow as a bundle into the developing brain. The 
growth cones of these axons have to navigate over 
a long distance and make a number of highly spe- 
cific choices. 
We would like to understand what signals 
guide axons to their proper destinations and how 
these signals are generated, received, and inter- 
preted. To address these questions, we have 
screened for mutations that perturb the projec- 
tion pattern of photoreceptor cells at early devel- 
opmental stages, when axons enter the brain. We 
have found a number of mutants with severely 
abnormal patterns of axon ingrowth. The devel- 
opmental and genetic characterization of this ma- 
terial is in progress. 
Innervation, 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. Cell death in 
the absence of incoming projections is a dramatic 
example of how innervation can affect develop- 
mental decisions, and many neurological dis- 
orders are thought to arise from defective interac- 
tions between neurons and their targets. In 
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