Genetic Control of Segmentation and Segmental Pattern Formation in Drosophila 
regulate the expression of the stem cell-specific 
proneural genes of the AS-C. Finally, we are work- 
ing to understand better the prepattern that gov- 
erns pattern formation in imaginal discs — the 
distinct pouches of cells that are set aside during 
embryogenesis, proliferate extensively during 
larval development, and give rise to adult struc- 
tures such as the wing, leg, and eye. 
Regulation of Segmentation Gene 
Expression 
During early Drosophila development, small 
batteries of genes are expressed in rapid succes- 
sion to establish the segmental prepattern. The 
first genes expressed in a periodic pattern are the 
pair- rule genes, deployed in one stripe per every 
two segments. Previous studies have shown that 
the generation of some pair-rule patterns is de- 
rived directly from other such patterns, i.e., 
stripes carving more stripes, but a select group of 
pair-rule patterns is generated from the aperiodic 
pattern of the gap proteins, a small number of 
transcription factors expressed in broad partially 
overlapping zones of the early embryo. The hairy 
gene is one pair-rule gene regulated in this way. 
Our laboratory is trying to determine how the 
many gap genes carve the hairy pattern into 
stripes. One unexpected observation is that sev- 
eral of the gap proteins appear to act by repress- 
ing hairy transcription in discrete regions of the 
embryo, as opposed to activating specific stripes. 
The elucidation of the direct activators and re- 
pressors of hairy transcription and their sites of 
action within the upstream regulatory DNA of the 
hairy locus is a major goal of our present work. 
Segmental Pattern Regulation and 
Proneural Gene Expression 
The stripes of pair-rule gene products are not 
sufficient to specify the precise location of indi- 
vidual cells of any tissue or organ. Rather, multi- 
ple regulatory systems that determine segment 
number, polarity, identity, and germ-layer posi- 
tion must all converge upon subsets of other 
genes to specify the three-dimensional coordi- 
nates of individual cells. To achieve a better un- 
derstanding of this process, we have begun a de- 
tailed study of the spatial regulation of two genes 
of the AS-C, which promote neural development. 
Once the early prepatterns are in place, the posi- 
tional information they provide determines 
where the genes of the AS-C will be active. We 
have found that the products of the achaete and 
scute genes, which themselves are regulatory 
proteins, are expressed at distinct dorsoventral 
positions of the neuroectoderm in both a seg- 
mentally repeating and segmentally modulated 
pattern. The identification of the direct regula- 
tors of AS-C gene expression and the sites through 
which they act is a second major thrust of the 
laboratory. 
Prepatterns in Imaginal Discs 
One of the best known but least understood 
aspects of Drosophila development concerns the 
morphogenesis of adult structures from the larval 
imaginal tissues. The eyes, wings, legs, antennae, 
and other appendages are derived from these sacs 
of cells, which undergo extensive changes during 
larval growth and pupation. Many of the genes 
that control the pattern of the relatively small 
numbers of cells of each embryonic segment also 
control the final morphology of the adult. The 
molecular prepatterns that govern eye, wing, leg, 
and antennal development are not well known. 
Our laboratory has embarked on a detailed study 
of certain genes expressed in imaginal discs, such 
as hairy, the AS-C, and others, in order to define 
better the imaginal prepatterns and the morpho- 
genetic processes they control. 
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