NecHns and Integrins: The Molecular Basis of Cell-Substratum Adhesion 
receptors in interactions with the cytoskeleton. 
We have also obtained detailed structural infor- 
mation about the cytoskeletal protein talin, 
which is a primary candidate for interactions with 
integrins. Further progress along these lines 
should help explain the effects of cell adhesion 
on cell structure and behavior. 
" Using the methods of cell and molecular biol- 
ogy, we are studying the structure and function of 
fibronectins and integrins, their interactions, and 
their roles in various physiological processes, in- 
cluding development, blood clotting, inflamma- 
tion, wound healing, and cancer. We observe reg- 
ulated expression of these molecules during 
these processes, and it is clear that these mole- 
cules are crucial for the appropriate behavior of 
cells. For instance, altered expression of both fi- 
bronectins and integrins in tumor cells contrib- 
utes to their wayward behavior, and expression of 
these proteins is altered during wound healing. 
We have used recombinant DNA methods to pro- 
duce specific and modified forms of fibronectins 
and integrins and investigate the ways in which 
they affect the behavior of individual cell types 
such as platelets. 
To extend our understanding of the roles of 
fibronectins and integrins in intact organisms, we 
use genetic analyses in two animal systems. We 
are analyzing the role of integrins during the de- 
velopment of Drosophila melanogaster, a fruit 
fly that is suitable for genetic analyses. Flies with 
mutations in genes encoding integrins have de- 
fects in embryonic development, in muscle func- 
tion, and in the development of wings and eyes. 
Analyses of these defects provide insight into the 
functions of these proteins. We have also gener- 
ated strains of mice that are mutant for fibronec- 
tins, and we plan to investigate the effects of 
these mutations on hemostasis, thrombosis, 
wound healing, and tumor development. We are 
also working to generate mice with mutations in 
integrins and in other molecules involved in cell 
adhesion. 
These studies should- provide a deeper under- 
standing of the molecular basis of cell adhesion 
and its involvement in physiological and patho- 
logical processes. This understanding, in turn, 
should provide opportunities for therapeutic 
treatments of diseases such as thrombosis and 
cancer. 
Opposite: Sections of the eyes o/Drosophila melanogaster, showing the regular array of photore- 
ceptors attached to a basement membrane in normal ( wild-type ) retina and the disruption of this 
organization in eyes of flies with mutations in integrins. 
Research of Susan Zusman and Richard O. Hynes. 
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