of tim mutants resemble those of per° mutants, it is 
possible that tim alters rhythmicity because it af- 
fects per transcription. It is equally possible that tim 
affects per indirectly, by eliminating an upstream 
biological clock. 
Genetic Control 
of Neuromuscular Development 
Now recognized in Drosophila are seven zygoti- 
cally required genes whose absence results in over- 
production of neuroblasts at the expense of epider- 
moblasts. Recently, from collaborative studies with 
Dr. Thomas P. Maniatis and his colleagues (Harvard 
University), Dr. Young's laboratory has discovered 
for these genes a very different role. Each gene is 
essential for correct patterns of mesodermal 
development. 
Mesodermal expression of all of the neurogenic 
genes has been observed, beginning at about the 
time of neuroblast delamination in the embryo. Loss 
of any of the neurogenic genes results in overpro- 
duction of certain mesodermal cells that normally 
give rise to precursors of muscle. This hyperplasia 
in the mutants affects at least the somatic mesoderm, 
and probably occurs at the expense of another me- 
sodermal cell type(s), in a fashion similar to the 
switching of cell fates in the ectoderm. In some mu- 
tants, cell fusions required for formation of multi- 
nucleate muscle are also eliminated. Strong effects 
on differentiation of visceral mesoderm also have 
been seen. So far there is no indication that these 
mesodermal effects depend on aberrant develop- 
ment of the associated ectoderm in the mutants. 
The results suggest that the seven genes may work 
together to influence cell fate choices undertaken 
independently in mesoderm and ectoderm. Rather 
than provide specific instructions about what a 
cell's final fate is to be, the products of these genes 
may allow cells to choose between alternative cell 
pathways common to many tissue types, with the 
ultimate fate of the cell determined by the local his- 
tory of the tissue involved. 
In other collaborative work with Dr. Jose Campos- 
Ortega (University of Koln) , the laboratory has in- 
vestigated the molecular details underlying genetic 
interactions between two neurogenic genes. Notch 
and Delta. Both genes code for transmembrane pro- 
teins containing several extracellular EGF (epider- 
mal growth factor)-like elements. Aberrant develop- 
ment has been linked to single-amino acid 
substitutions in EGF elements of Notch protein, and 
some of these mutations are genetically suppressed 
by single-amino acid substitutions in EGF elements 
of the Delta protein. The collaborative studies have 
shown that these simple substitutions measurably 
alter interactions between Notch and Delta proteins 
expressed on the surfaces of cultured cells. Some of 
the results suggest that effects on development are 
due to altered intracellular signaling by the Notch 
protein in response to novel, direct interaction with 
Delta. (The above studies of neuromuscular devel- 
opment have been supported by a grant from the 
National Institutes of Health.) 
Dr. Young is also Professor of Genetics at the 
Rockefeller University. 
Books and Chapters of Books 
Abmayr, S.M., Michelson, A.M., Corbin, V., Young, 
M., and Maniatis, T. 1992. nautilus, 2i Drosophila 
member of the myogenic regulatory gene family. 
In Neuromuscular Development and Disease 
(Kelly, A.M., and Blau, H.M., Eds.). New York: 
Raven, pp 1-16. 
Articles 
Corbin, Y., Michelson, A.M., Abmayr, S.M., Neel, V., 
Alcamo, E., Maniatis, T., and Young, M.W. 
1 99 1 . A role for the Drosophila neurogenic genes 
in mesoderm differentiation. Cell 67:31 1-323- 
Sehgal, A., Price, J., and Young, M.W. 1992. On- 
togeny of a biological clock in Drosophila me- 
lanogaster. Proc Natl Acad Set USA 89:1423- 
1427. 
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