the Fushi tarazu protein activates after binding to 
the same DNA sites. The function of another class 
of transcription factors encoded by the so-called 
gap genes has also been investigated by Dr. 
Desplan's laboratory. These zinc finger proteins act 
early in development to set up segmentation. Bind- 
ing sites for the Kriippel and Hunchback proteins 
have been defined in the hunchback promoter, and 
their function is now being tested in vivo. 
During the development of an organism, infor- 
mation for the determination of different cell types 
becomes unevenly distributed in cells and tissues. 
In Drosophila the transcript of the bicoid (bed) 
gene is localized to the anterior end of the oocyte; 
this results in a concentration gradient of bed pro- 
tein in the developing embryo. The product of the 
gene exuperantia (exu) is required for localizing 
the bed transcript and for the formation of normal 
sperm in male flies. The laboratory of Assistant In- 
vestigator Tulle Hazelrigg, Ph.D. (University of 
Utah) has cloned the exu gene and is studying how 
it functions in oogenesis to bring about the subcel- 
lular localization of the bed RNA, and also in sper- 
matogenesis. Patterns of gene expression within a 
given tissue can be influenced by regulatory se- 
quences in the DNA flanking a gene. When a gene 
is moved to a new location in the genome, other 
regulatory sequences can cause its expression in 
novel patterns. For example, the DNA flanking a re- 
located copy of the white gene causes a restriction 
in its expression to certain cells in the eye. Analysis 
of this flanking DNA by Dr. Hazelrigg's laboratory 
has revealed regulatory sequences that appear to 
act in conjunction with regulatory sequences 
within the promoter of the white gene to bring 
about this pattern of expression. 
The laboratory of Assistant Investigator Norbert 
Perrimon, Ph.D. (Harvard Medical School) is study- 
ing the molecular biology of the genes involved in 
pattern formation. Two developmental systems are 
under investigation: 1) the genes involved in the 
determination of the antero-posterior axis intra- 
segmental patterning of the organism and 2) genes 
involved in the determination of a small number of 
cells in the central nervous system. This laboratory 
is also developing techniques for the ectopic activa- 
tion of genes in order to manipulate the expression 
of the gene products involved in pattern formation 
and to contribute to the growing understanding of 
how developmental genes act. 
Two homeotic genes, abd-A and Abd-B, that dic- 
tate the fate of cells in the abdominal segments of 
Drosophila melanogaster are under study in the 
laboratory of Assistant Investigator Shigeru Sakonju, 
Ph.D. (University of Utah). The gene structures for 
both abd-A and Abd-B have been characterized. 
The abd-A gene encodes a single protein that binds 
specifically to the promoter region of another 
homeotic gene, Antennapedia. The transcriptional 
regulation of Antp by abd-A in Drosophila is being 
investigated. Two genetic functions have been 
mapped to the Abd-B gene. Molecular analysis indi- 
cates that four overlapping transcripts are gener- 
ated from the Abd-B gene. One transcript encodes a 
protein that provides a function needed in the fifth 
to eighth abdominal segments; the other three 
transcripts encode a protein required in the ninth 
abdominal segment. 
Assistant Investigator Philip A. Beachy, Ph.D. (The 
Johns Hopkins University) and his colleagues have 
focused their studies on identifying morphogenetic 
genes that are involved in metameric pattern forma- 
tion in Drosophila. Milligram quantities of the 
DNA-binding protein encoded by the homeotic 
gene Ultrabithorax (Ubx) have been purified, and 
methods have been developed to separate bound 
from unbound DNA molecules. Several Drosophila 
cell lines have been developed that express Ubx 
proteins under inducible control and provide an 
additional route to the identification of target genes 
and to testing the significance in vivo of the bind- 
ing sites. Finally, several genomic regions have been 
found to contain potential targets for Ubx regula- 
tion through examination of the expression pattern 
of an introduced P-galactosidase gene. 
Members of the laboratory of Investigator Mi- 
chael W Young, Ph.D. (The Rockefeller University) 
are studying the genes that control certain biologi- 
cal rhythms and the development of the nervous 
system. The distribution of the proteins expressed 
by two genes, Notch and per, has been determined. 
The Notch protein has been found on several cell 
types, chiefly of ectodermal origin, both before and 
after terminal differentiation. The distributions un- 
covered are consistent with their having a role in 
position-dependent development through the es- 
tablishment and maintenance of specialized cell 
contacts among differentiating cells. Earlier genetic 
studies had demonstrated a requirement for per in 
the nervous system for the production of circadian 
rhythms. The per protein is produced in the eye 
and optic lobes of the brain and in the thoracic 
ganglia. The protein is also synthesized in the ring 
gland complex that produces a hormone that deter- 
mines the timing of eclosion. Abundant expression 
is also seen in gonadal tissue. 
Continued 
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