Johnson, J.E., Zimmerman, K., Saito, T., and An- 
derson, D.J. 1992. Induction and repression of 
mammalian achaete-scute homologue {MASH) 
gene expression during neuronal differentiation 
of PI 9 embryonal carcinoma cells. Development 
114:75-87. 
Michelsohn, A.M., and Anderson, D.J. 1992. 
Changes in competence determine the timing of 
two sequential glucocorticoid effects on sym- 
pathoadrenal progenitors. Neuron 8:589-604. 
Mori, N., Schoenherr, C, Vandenbergh, D.J., and 
Anderson, D.J. 1992. A common silencer ele- 
ment in the SCO 10 and type II Na^ channel genes 
binds a factor present in nonneuronal cells but 
not in neuronal cells. Neuron 9:45-54. 
Vandenbergh, D.J., Mori, N., and Anderson, D.J. 
1991. Co-expression of multiple neurotransmit- 
ter enzyme genes in normal and immortalized 
sympathoadrenal progenitor cells. Dev Biol 
148:10-22. 
CELL FATE CHOICES IN DEVELOPMENT 
Spyridon Artavanis-Tsakonas, Ph.D., Investigator 
Dr. Artavanis-Tsakonas and his collaborators have 
been investigating the mechanisms of cell communi- 
cation that control the choice of cellular fates in 
Drosophila development. They are particularly in- 
terested in how these rules apply to the nervous sys- 
tem and have been studying the molecular biology 
and genetics of a group of genes that are involved in 
cell fate choices in neural development. 
Genes Controlling Cell Fate Choices 
A variety of studies have indicated that the ability 
of a cell to choose between an epidermal and neuro- 
nal developmental pathway depends on interactions 
between neighboring cells. In Drosophila, the 
Notch locus, which was shown several years ago by 
the Artavanis-Tsakonas group to code for a trans- 
membrane protein with homology to the epidermal 
growth factor (EOF) , is known to play a central role 
in this process. Phenotypic analysis of many Notch 
alleles, as well as in situ hybridization and antibody 
localization experiments, have shown that in addi- 
tion to neuronal differentiation, Notch controls the 
differentiation of numerous tissues. The accumu- 
lated evidence indicates that the Notch gene prod- 
uct functions in a rather general signal transduction 
mechanism required for many different types of cell 
fate decisions. Many if not all of the regulative 
events required throughout development for the 
correct differentiation of neighboring precursor 
cells into distinct developmental paths appear to 
depend on TVofc^-mediated signals. 
The notion that Notch plays a role in a cell com- 
munication mechanism implies the existence of sev- 
eral interacting components. In an attempt to un- 
derstand the biochemical nature of Notch and 
identify interacting partners, much of the research 
effort of the Artavanis-Tsakonas laboratory is ad- 
dressed to the dissection of the genetic circuitry in 
which Notch is integrated. Based on several criteria, 
a group of interacting genes have already been iden- 
tified and were operationally termed the "Notch 
group." So far this group consists of Notch, Delta, 
mastermind. Enhancer of split, deltex, and 
Serrate. The gene products of the Notch group were 
shown to code for nuclear and cytoplasmic as well 
as cell surface elements. During the past year the 
Artavanis-Tsakonas group has been studying the mo- 
lecular and genetic relationships among the 
members of the Notch group while continuing the 
search for additional elements involved in Notch- 
mediated cell communication. 
Notch, Delta, and Serrate 
Apart from Notch, two other Notch group 
members were shown to code for cell surface ele- 
ments: Delta and Serrate. Both code for transmem- 
brane proteins with extracellular domains display- 
ing homology to EGF, and both were shown to 
interact with Notch molecularly as well as geneti- 
cally. Using a cell aggregation assay, the Artavanis- 
Tsakonas group demonstrated that Notch is capable 
of interacting with Delta and Serrate y'i^l their extra- 
cellular domains. 
Through an extensive deletion mutagenesis of the 
extracellular domain of Notch, the group further 
found that of the 36 EGF repeats of Notch, only two 
(11 and 12) are both necessary and sufficient to 
mediate interactions with Delta and Serrate. Fur- 
390 
