Drosophila Behavior and Neuromuscular Development 
ability to form a set of early acting developmental 
signals, so we are using the mutations to mark, 
isolate, and characterize the products of these 
genes and putative developmental signals. Neu- 
rogenic mutations have been recovered at seven 
genetic loci: Notch, big brain, mastermind, 
neuralized. Delta, almondex, and Enhancer of 
split. 
Notch has been characterized more completely 
than any other gene in the neurogenic group. The 
gene produces a very large protein (2,700 amino 
acids) that is predominantly composed of an un- 
interrupted array of 36 copies of a hormone-like 
molecule, a relative of epidermal growth factor. 
The Notch protein spans the cellular membrane 
with the 36 hormone copies exposed to its neigh- 
bors. We suspect that the neighbors read that sig- 
nal and send signals to the TVo^c^-bearing cell in 
return to come up with the correct allocations of 
skin and nerve. Biochemical experiments have 
shown that the entire string of hormone copies is 
tethered to the cell's surface; thus signaling be- 
tween cells must be intimate. Only cells that can 
touch each other could communicate through 
such a protein. 
From work with temperature-sensitive muta- 
tions we know that Notch proteins are used to 
instruct development throughout embryonic, 
larval, and pupal life. Mutations altering the 
structures of individual hormone-like elements 
of the Notch protein have been examined to un- 
derstand the role each plays in early and late de- 
velopment. Of the 36 hormone repeats, no two 
are identical and, importantly, changes in differ- 
ent hormone elements produce different develop- 
mental abnormalities. Thus alternate parts of the 
Notch hormone string must be read as develop- 
ment unfolds. In part these specificities could al- 
low a cell to talk to changing neighbors from the 
time of cell birth to differentiation to form adult 
tissue. 
What do signals from these genes tell a cell to 
do? For several years it has been argued that gene 
action at Notch, Delta, big brain, almondex, 
neuralized, mastermind, and Enhancer of split 
stimulates an undifferentiated ectodermal cell to 
develop as an epidermal cell; the genes are ex- 
pected to provide a series of epidermalizing sig- 
nals during cell differentiation, with loss of func- 
tion generating a nerve cell. New work shows that 
this simple picture cannot be accurate. 
Notch proteins have now been found in cells 
giving rise to embryonic muscle. In Notch mu- 
tants, strong effects on muscle development are 
seen, with increased numbers of some muscle 
cell types generated, probably at the expense of 
others. Thus parallel changes in muscle, skin, and 
nerve development take place in Notch mutants. 
Of most significance, comparable effects on mus- 
cle development are seen with mutations of 
Delta, big brain, mastermind, almondex, En- 
hancer of split, and neuralized. 
We have learned three things from these stud- 
ies. 1) The developmental fates of many cell 
types are switched in neurogenic mutants. 2) The 
genes must provide differentiation signals that 
can be read by cells composing different germ 
layers, with no apparent overlap in the cells' final 
developmental fates. 3) The genes defined by the 
neurogenic mutations probably work together to 
form a single developmental pathway, which gen- 
erates a common differentiation signal in all cells 
affected in the mutants. This last conclusion fol- 
lows from our observation that any developmen- 
tal anomaly caused by loss of one gene in the 
group predicts a comparable developmental 
change upon loss of any other gene in the series. 
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