Drosophila Behavior and Neuromuscular Development 
tions to mark, isolate, and characterize the prod- 
ucts of these genes and putative developmental 
signals. Neurogenic mutations have been recov- 
ered 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. It 
produces a very large, 2 ,700-amino acid protein, 
predominantly composed of an uninterrupted 
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 neighbors. We 
surmise that the neighbors read that signal and, in 
return, tell the A'^orc^-bearing cell to come up 
with the correct allocations of skin and nerve. 
Since the entire string of hormone copies is teth- 
ered to the cell's surface, signaling between 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 de- 
termine the role each plays in early and late devel- 
opment. Of the 36 hormone repeats, no two are 
identical, and changes in different hormone ele- 
ments produce different developmental abnor- 
malities. This must mean that alternate parts of 
the Notch hormone string are 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 into adult 
tissue. 
What do signals from these genes tell a cell to 
do? For several years gene action at Notch, Delta, 
big brain, almondex, neuralized, mastermind, 
and Enhancer of split have been assumed to stim- 
ulate an undifferentiated ectodermal cell to de- 
velop as an epidermal cell. The genes are thought 
to provide a series of epidermalizing signals dur- 
ing cell differentiation, with loss of function gen- 
erating a nerve cell. New work in our laboratory 
shows this simple picture to be inaccurate. Notch 
proteins have now been found in cells giving rise 
to embryonic muscle. In Notch mutants, strong 
effects on muscle development are seen, with in- 
creased numbers of some muscle cell types gen- 
erated, probably at the expense of others. Thus 
parallel changes in muscle, skin, and nerve devel- 
opment take place in Notch mutants. Of most sig- 
nificance, comparable effects on muscle develop- 
ment are seen with mutations of Delta, big brain, 
mastermind, almondex. Enhancer 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 cells 
composing different germ layers can read, with 
no apparent overlap in the final developmental 
fates; and 3) the genes defined by the neurogenic 
mutations probably work together to form a sin- 
gle developmental pathway, which generates a 
common differentiation signal in all cells af- 
fected in the mutants, since any developmental 
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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