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GENETIC CONTROL OF PATTERN FORMATION IN DROSOPHILA AND OTHER INSECTS 
Sean B. Carroll, Ph.D., Assistant Investigator 
During animal development, cells of the growing 
embryo become organized into structures of widely 
varying number, size, shape, composition, and 
function. Genetic and embryological studies of a 
model animal, the insect Drosophila melanogas- 
ter, have shown that the specification of the overall 
body plan, the formation of complex arrays of tis- 
sues and organs, and the assignment of individual 
cell fates occur in a highly ordered temporal se- 
quence and spatial pattern. Genetic screens for pat- 
tern-disrupting mutations have identified many of 
the loci that influence the size, shape, number, and/ 
or function of body structures and have catalyzed an 
integrated molecular and embryological approach 
to understanding the control and function of pat- 
tern-regulating genes and the overall logic of devel- 
opmental processes. More recently, the scope of this 
"molecular embryology" has widened toward the 
analysis of the evolution of developmental pro- 
cesses in diverse animals, with the goal of identify- 
ing common themes in body design and understand- 
ing the genetic basis of morphological evolution. 
Research is currently centered on the cell biology 
and genetics of pattern formation in animals at three 
levels. The first involves the formation of large-scale 
patterns in Drosophila and, more specifically, the 
regulation and function of the more globally acting 
genes that establish segment number and segmental 
pattern in the larva and control appendage forma- 
tion in the adult. The second level addresses pattern 
formation on a finer scale within segments and ap- 
pendages, using both the Drosophila nervous sys- 
tem and, more recently, butterfly wing color pat- 
terns as models. The third level is broadly 
concerned with the molecular and developmental 
basis for the evolution of both global and fine-scale 
patterns among insects. 
Pair-rule Genes Integrate Segment 
Formation with Intrasegmental 
Pattern Formation 
The first sign of the future segmental organization 
of the Drosophila embryo is the expression of the 
pair-rule genes in alternating stripes encircling the 
early blastoderm embryo. Two fundamental ques- 
tions concerning the regulation and function of 
these genes are of the most interest: 1) How are 
these periodic patterns of gene expression initially 
established in the embryo? 2) How do the pair-rule 
genes control the subsequent segmental organiza- 
tion of the developing embryo? 
Using the hairy pair-rule gene as a model for the 
regulation of periodic gene expression, several labo- 
ratories have shown that the aperiodically expressed 
gap genes establish the striped pattern of hairy ex- 
pression. Each hairy stripe is regulated by separable 
cis-acting regulatory sequences upstream of the 
hairy gene. Jim Langeland has shown that the linear 
order of the cis-acting regulatory sequences is con- 
served in distant Drosophila species {D. virilis) and 
that all of the gap proteins appear to regulate the 
same stripe boundaries. Even more striking was the 
finding that these D. virilis sequences, when trans- 
formed into D. melanogaster, are capable of driv- 
ing the normal pattern of seven hairy stripes. By 
localizing stretches of conserved regulatory se- 
quence, a minimal regulatory element for one hairy 
stripe has been identified that is repressed by two 
CELL BIOLOGY AND REGULATION 33 
