Morphogen Gradients and the Control of Body 
Pattern in Drosophila 
Gary Struhl, Ph.D. — Associate Investigator 
Dr. Struhl is also Associate Professor of Genetics and Development at Columbia University College of 
Physicians and Surgeons. He received B.S. and M.S. degrees in biology from the Massachusetts Institute of 
Technology and his Ph.D. degree in genetics from the University of Cambridge, England. His graduate 
studies were carried out with P. A. Lawrence at Cambridge. Before joining the faculty at Columbia, he 
conducted molecular and genetic studies in Drosophila with T. Maniatis at Harvard University. In addition 
to several fellowships, he received the McKnight Neuroscience Development Award. 
MOST animals large enough for us to see with 
the naked eye consist of billions or trillions 
of individual cells arranged in extremely com- 
plex and highly conserved patterns. To generate 
such patterns, cells in a developing organism 
must know where they are and choose what to do 
based on this information. Research in our labora- 
tory is directed toward understanding how such 
spatial information is generated and interpreted 
during development. 
For many years considerable attention has been 
given to the concept that gradients of diffusible 
"form-generating" substances, or morphogens, 
might provide this spatial information. For exam- 
ple, a localized source of a diffusible, but unsta- 
ble, morphogen would generate a stable gra- 
dient, which could, in turn, provide a series of 
concentration thresholds that would determine 
distinct cellular behaviors (e.g., the develop- 
ment of particular pattern elements) as a function 
of distance from the source. 
During the past 10-15 years, the pioneering 
embryologic and genetic experiments of Chris- 
tiane Niisslein-Volhard and her colleagues have 
established that several distinct morphogens 
specify the basic body plan of the fruit fly Dro- 
sophila early in development. One of these, the 
protein product of the gene bicoid {bed), con- 
trols most aspects of the anterior pattern of the 
body, while the products of two other genes, 
nanos (nos) and torso (tor), seem to specify the 
pattern of the remaining posterior and terminal 
portions. Our principle aim is to determine the 
roles and modes of action of each of these differ- 
ent morphogen systems. 
Control of Anterior Body Pattern 
by the bed Morphogen 
Dr. Niisslein-Volhard and her colleagues estab- 
lished that transcripts of the bed gene are synthe- 
sized and then transported to the anterior pole of 
the egg during oogenesis. Following fertilization, 
these tightly localized transcripts are translated, 
and the resulting protein diffuses from its site of 
synthesis, generating a concentration gradient. 
To determine how the bed protein gradient dic- 
tates anterior body pattern, we have sought to 
identify direct targets of bed action and to deter- 
mine the mechanisms that allow different con- 
centrations of protein to control how these tar- 
gets respond. 
In an initial series of experiments, we estab- 
lished that the bed gradient is responsible for 
generating an opposing gradient of another regu- 
latory protein, caudal {cad). Although we have 
yet to determine the exact mechanism by which 
this response occurs, our data suggest that bed 
protein may repress translation of maternally de- 
rived cad transcripts that are ubiquitously distrib- 
uted in the early embryo. More recently, we have 
identified a second target of bed action, and in 
this case determined the mechanism involved. 
The target is a zygotic regulatory gene, hunch- 
back {hb), which is normally activated in a well- 
defined anterior portion of the early embryo. We 
have shown that bed protein directly binds and 
transcriptionally activates the hb gene in a fash- 
ion that depends critically on bed protein con- 
centration. Hence, the anteroposterior gradient 
of bed protein provides a distinct threshold dic- 
tating where the hb gene is expressed. 
These and other experiments have also pro- 
vided evidence that the bed gradient triggers a 
series of other distinct responses by the same 
mechanism — each response governed by the par- 
ticular binding affinity of a different target gene 
for the bed protein. The ability of the bed protein 
to control the patterns of subordinate signaling 
molecules by at least two distinct mechanisms, as 
well as the demonstration that it acts directly on 
several distinct targets, clearly indicates how the 
graded distribution of a single morphogen can 
provide a complex set of instructions for organiz- 
ing body pattern. 
Control of Posterior Body Pattern by the 
nos and hb Morphogens 
The development of posterior pattern is largely 
dependent on the nos morphogen, which ap- 
pears to spread from a tightly localized source at 
the posterior pole during early embryogenesis. It 
was initially thought that this factor operates like 
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