Understanding How Eggs Work 
When these antibodies are used, eggs that previ- 
ously appeared normal in the microscope can 
suddenly be seen to have specific defects. Such 
molecular biological studies allow us to under- 
stand in much greater detail vv^here in an egg par- 
ticular gene products are located, where they go 
as development begins, and what role they are 
4ikely to play in the process. 
Transporting Materials Into Eggs 
One project of our research group concerns 
how the massive amount of material found in an 
egg actually gets there. In the fruit fly most of the 
egg contents are piped in from 15 nearby cells 
called nurse cells. Four of these cells are attached 
directly to the egg by special "pipes" made of the 
same material as the outer surface of cells, and 
the remaining 1 1 are attached to other nurse cells 
by similar pipes. Thus some of the material in an 
egg has been shipped through as many as four 
nurse cells on the way to its destination. Nurse 
cells not only control somehow the rate and direc- 
tion of transport, but even select certain products 
for priority delivery, moving them well ahead of 
the majority of the egg's contents. 
To learn more about the equipment flies use to 
make their eggs, we identified some mutant 
strains in which either the connections between 
nurse cells and egg did not form properly, or ma- 
terial did not flow very well. We have now stud- 
ied one mutant in some detail. When mother flies 
lack this gene, they are able to attach on average 
only four nurse cells to their eggs. As a result the 
eggs usually do not grow properly and are unable 
to function. Rarely, a developing egg becomes 
connected to as many as 11 nurse cells, and a few 
of these eggs can develop, so the affected females 
are not completely sterile. 
We determined the structure of the protein that 
was missing in the mutant, and were surprised to 
learn that it was very similar to one found in large 
amounts just under the surface of human and 
other mammalian red blood cells. This protein, 
called "adducin," has been studied for some time 
by Vann Bennett (HHMI, Duke University). It has 
been found at various levels in many types of cell, 
where it is thought to strengthen cell membranes 
by acting as a kind of skeleton supporting the 
floppy lipid bilayer. Red cell adducin is thought 
to act with other membrane skeleton proteins to 
mold red cells into their characteristic concave 
disk shape and to lend the physical properties 
that let them pass through small capillaries. As 
with many human proteins, however, the actual 
function is uncertain because the effects of re- 
moving a red cell's adducin are unknown. 
At present we are attempting to learn in detail 
what adducin does to help nurse cells and eggs 
hook up properly. The pipes form during cell di- 
vision. Normal daughter cells separate when a re- 
gion of membrane clamps down as though con- 
stricted by a knot from outside. Eventually the 
two cells are choked off completely. During the 
last few divisions that give rise to the nurse cells 
and egg, these constrictions simply stop short, 
leaving a small interconnecting region of cell 
membrane. This junction subsequently forms 
into a pipe. In the adducin mutants, many of the 
constrictions are unable to stop, so cells that 
should have built a connecting pipe become com- 
pletely separated. The pipes that do form in the 
mutant are much weaker looking than normal, 
may not transport materials very well, and appear 
susceptible to breakage. 
Understanding how adducin contributes to 
fruit fly egg production may provide insight into 
the details of how it works in humans. The mu- 
tant flies also have several other abnormalities 
besides their inability to connect nurse cells and 
the egg properly, indicating that the function of 
adducin can be studied in a variety of different 
situations. Experimenters can now make what- 
ever changes in the protein's structure they wish, 
introduce a modified gene encoding the altered 
protein back into the mutant strain of fruit fly, 
and see if the modified protein will "rescue" 
some or all of the fly's problems or create new 
ones. This approach can be applied to the many 
different gene products that make up a fruit fly egg. 
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