Genetic Control of Morphogenesis in Drosophila 
mains to be characterized, along with the intra- 
cellular consequences of this signaling event. 
Regulatory Functions of Homeotic Genes 
Homeotic genes play a primary role in conver- 
sion of the spatial information generated by the 
earlier-acting segmentation genes into morpho- 
logical structure. The products of homeotic 
genes direct morphogenesis in a manner that 
produces the diversity of structures distinguish- 
ing the segments. This task is presumably ac- 
complished by differential regulation of target 
genes, though the identities of these targets 
and the mechanisms by which homeotic genes 
achieve their biological specificity remain 
largely unknown. 
We have studied in detail the DNA sequence- 
recognition properties of homeodomains from 
the homeotic genes Deformed and Ultrabitho- 
rax. While these domains are very closely re- 
lated, we have demonstrated clear differences in 
DNA sequence preferences that lead to moderate 
differences in affinity for individual binding 
sites. Our recent work demonstrates that these 
differences in sequence preference map to the 
two DNA-contacting portions of the homeodo- 
main. Even small differences in binding to indi- 
vidual sites can lead to large differences in regula- 
tory effect when multiple sites are present. This is 
due to cooperative binding of homeodomain pro- 
teins to multiple sites, a property we have studied 
extensively for the Ultrabithorax protein. Dif- 
ferences in DNA sequence preference by homeo- 
tic gene products may thus account for a substan- 
tial part of the biological specificity of homeotic 
gene function. 
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