Genetic Control of Pattern Formation in Drosophila 
rule genes are generated by the aperiodic pat- 
terns of gap proteins, a handful of transcription 
factors expressed in broad, partially overlapping 
regions of the early embryo. 
Three aspects of pair-rule gene regulation and 
function are under study. First, we wish to deter- 
mine the molecular mechanisms of gap gene reg- 
ulation of the pair-rule hairy gene. Second, we 
want to know how the pair-rule genes regulate 
the spatial expression of proneural genes during 
early formation of the nervous system. And third, 
we are investigating whether the same sort of seg- 
mentation genes function in insects with differ- 
ent styles of early development (e.g., beetles and 
butterflies) . To this end, we are now isolating gap 
and pair-rule genes from other insects and arthro- 
pods to study their embryonic function. 
Proneural Genes and Early Neurogenesis 
Once the embryo is subdivided by the segmen- 
tation genes, the formation of different tissues be- 
gins. One of the earliest events in embryogenesis 
is the segregation of the central nervous system 
precursor cells (neuroblasts) from the overlying 
ectoderm. The proneural genes, which are 
named for their role in promoting the neural over 
the epidermal pathway in the insect embryonic 
ectoderm, are expressed in segmentally repeat- 
ing clusters of 4-6 cells. A single proneural- 
expressing neuroblast will segregate from each 
cluster. 
We have recently determined that the estab- 
lishment of proneural gene expression in these 
clusters is almost entirely regulated by up to 
eight pair-rule genes (all of which appear to be 
nuclear regulatory proteins) and an unknown 
number of genes acting along the dorsoventral 
axis. This demonstrates that the pair-rule genes 
are not simply involved in regulating the expres- 
sion of other segmentation genes, but also direct 
the expression of genes that govern the behavior 
of small groups of cells. They serve to integrate 
the global regulatory system governing segmenta- 
tion with the local regulatory system that speci- 
fies tissue architecture. 
The pair-rule genes are not sufficient to specify 
individual cell fates, only the position of pro- 
neural cell clusters. Interactions between cells 
within each cluster determine their neural or epi- 
dermal fate. We have shown that the so-called 
neurogenic genes — a handful of loci that encode 
a variety of different proteins involved in cell sur- 
face interactions, signal transduction, and gene 
regulation — are required to single out just one 
neuroblast from the proneural cluster and pre- 
vent the other cluster cells from entering the 
neural pathway. 
Development and Evolution of Insect 
Appendages 
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 structures are derived from sacs of cells 
that undergo extensive growth and morphogene- 
sis during the larval and pupal stages. We are 
most interested in the development of the wing. 
We have recently shown that the product of the 
vestigial gene is precisely expressed in those 
cells of the imaginal wing disc that will form the 
actual flight appendage and is not expressed in 
the other disc cells that will form structural com- 
ponents of the thorax. In the absence of vestigial 
gene function, fruit flies are wingless, suggesting 
that vestigial plays a special role in the develop- 
ment of wings from imaginal tissues. Further stud- 
ies into the regulation of vestigial expression in 
Drosophila may provide some interesting clues 
to the evolution and function of the vestigial 
gene in winged and wingless insects. 
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