Genetic Control of Segmentation and Segmental 
Pattern Formation in Drosophila 
Sean B. Carroll, Ph.D. — Assistant Investigator 
Dr. Carroll is also Assistant Professor of Molecular Biology, Genetics, and Medical Genetics at the Univer- 
sity of Wisconsin- Madison. He obtained his B.A. degree in biology from Washington University in St. Louis 
and his Ph.D. degree in immunology from Tufts University School of Medicine in Boston. He received 
postdoctoral training in developmental genetics with Matthew Scott at the University of Colorado. In ad- 
dition to his central work on pattern formation in Drosophila, Dr. Carroll has also conducted basic re- 
search on new types of snake antivenoms that are now under evaluation as potential pharmaceuticals. 
His honors include the NSF Presidential Young Investigator Award. 
VIRTUALLY every animal species can be distin- 
guished by its external and/or internal ap- 
pearance, its morphology. Gross similarities in 
external or internal organization usually reflect 
an evolutionary relationship between animals. 
Widespread similarities in body organization may 
reflect a common evolutionary origin of a large 
number of w^ell-diversified species. For example, 
a segmentally organized body plan, present in an- 
nelids (e.g., earthworms), arthropods (lobsters, 
spiders, insects) , and to a lesser degree in verte- 
brates (snakes, mice, humans), is one of the most 
general forms of organization in the animal king- 
dom. Evolutionary biologists believe that modifi- 
cations of the basic repeating segmental pattern 
found in earthworms and millipedes, for exam- 
ple, have led to the diverse array (perhaps more 
than 1 million species) of arthropods found to- 
day. For instance, it is thought that a gradual re- 
duction in leg number on the more posterior seg- 
ments of a many-legged animal has led to the 
present-day typical insect body plan, with only 
three pairs of legs protruding from the thorax fol- 
lowed by a legless abdomen. 
To understand how body patterns evolve, we 
must first learn about how body plans develop. 
To this end, we and several other HHMI laborato- 
ries are engaged in a detailed study of the genetic 
program that guides the development of the fruit 
fly Drosophila melanogaster. We focus on those 
genes that are critical to the organization of the 
segmental outline of embryo and adult, control- 
ling the overall pattern and function of body seg- 
ments. The wealth of genetic information gath- 
ered over the past 70 years and the explosion of 
Drosophila embryology and molecular biology 
over the past 1 0 years make it the best complex 
animal model for understanding the genetic regu- 
lation of cell behavior and the three-dimensional 
organization of tissues, organs, and entire 
organisms. 
Gene Activity During Drosophila 
Development 
The genetic control of pattern formation can be 
broken down conceptually into at least three 
phases. The first consists of a molecular prepat- 
tern, revealed as chemical changes taking place 
in different regions of the animal that foreshadow 
the cellular events to follow. For example, in the 
Drosophila embryo, certain key proteins come to 
be expressed in stripes, which represent the seg- 
mental divisions to form later. The second phase 
of segmental pattern formation involves the es- 
tablishment of a segmentally repeating array of 
stem cells within the diff'erent germ layers that 
give rise to the different tissues of the animal. For 
example, genes such as those of the achaete- 
scute complex (AS-C) are activated only in the 
stem cells of the central and peripheral nervous 
system. Finally, in the third phase, these stem 
cells divide, giving rise to the full complement of 
differentiated cells that make up different tissues 
and organs and express distinct structural genes 
to carry out their specialized tasks. 
From molecular prepattern to stem cell forma- 
tion to the differentiation of their progeny, there 
is a flow of genetic information. The prepattern 
specifies the spatial domains of genes that are ac- 
tivated in stem cells, and these genes in turn regu- 
late cell-type-specific gene expression. Our labo- 
ratory is interested in the genetic basis of this 
information flow, how it operates and is regu- 
lated. From the level of overall body organization 
to the molecular details of gene regulation, we 
want to know which genes are key to pattern regu- 
lation, how they coordinate gene expression and 
cell behavior, and how they and the regulatory 
programs they belong to have changed in the 
course of the morphological diversification of 
animals. 
To this end, our laboratory focuses on three 
aspects of the genetic control of pattern forma- 
tion during Drosophila development. First, we 
are working on the molecular regulation of the 
pair-rule genes, the first genes expressed in a seg- 
mentally repeating prepattern. Second, we are 
studying how the early embryonic prepattern 
genes governing segment number, segment polar- 
ity, segment identity, and germ-layer specificity 
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