Transcription Control During Early 
Drosophila Development 
Claude Desplan, Ph.D. — Associate Investigator 
Dr. Desplan is also Associate Professor and Head of the Laboratory of Molecular Genetics at the Rockefeller 
University. He graduated from the Ecole Normale Superieure de Saint Cloud in France. He received 
his D.Sc. degree from the University of Paris, working with Baty Moukhtar and Monique Thomasset 
at the INSERM on calcium regulation. He was a Maitre de Conference at the Ecole Normale Superieure 
de Fontenay until he moved to the University of California, San Francisco, to work as a postdoctoral 
fellow with Pat O'Farrell on the functions of homeodomain proteins during early development. 
ALL information required for the develop- 
ment of a fertilized egg into a complete or- 
ganism is contained in its own genetic material, 
contributed by both parents, and in products pro- 
vided by the mother as the egg is formed. Genetic 
studies on the fruit fly Drosophila have identi- 
fied most of the genes involved in the process of 
pattern formation. Many of these genes appear to 
encode transcription factors and to share some 
common protein motifs, such as homeodomains 
or zinc finger domains. The zygotic genome re- 
sponds to maternal organizing factors through a 
network of transcriptional regulators to set up the 
body pattern of the embryo. Many of the Drosoph- 
ila developmental genes have mammalian homo- 
logues expressed during embryogenesis. Thus it 
is likely that the mechanisms uncovered in flies 
are of general significance for the development of 
multicellular organisms. 
The goal of our laboratory is to understand the 
molecular mechanisms involved in the regula- 
tory interactions among developmental genes. In 
light of the complexity of the system, a produc- 
tive approach is, first, to characterize the molecu- 
lar interactions in vitro and, second, to design in 
vivo systems to test models consistent with prop- 
erties uncovered through the first approach. We 
are investigating the events leading to patterning 
in two major systems. One involves the establish- 
ment of the early anterior pattern, while the other 
is a structure-function analysis of a gene that con- 
trols later steps of development. Independent 
support will be sought for the research described 
in the first part of this report. 
Interactions Between Maternal 
and Zygotic Genes 
The maternal homeodomain-encoding gene bi- 
coid is one of the few examples of a morphogen. 
A concentration gradient of its protein product 
appears to control the establishment of the ex- 
pression pattern of the first set of zygotic genes, 
in particular the anterior gap gene hunchback 
{hb^. Using transgenic flies that carry artificial 
genes containing combinations of binding sites 
for the products of bicoid and hb, we have shown 
that the establishment of the simple hb pattern 
requires not only bicoid but also the synergistic 
participation of hb itself. This hb autoregulation 
may help explain the sharp, precise boundaries 
of its expression domain. It also has evolutionary 
implications for the development of other organ- 
isms that do not possess bicoid. 
The role of bicoid is not only to control hb 
expression but also to direct the expression of a 
set of newly discovered genes required for head 
formation. Using the same approach as described 
above, we have demonstrated that bicoid 
action is modulated by the maternal genes from 
the terminal torso group. These genes, which 
encode a cascade of kinases, appear to act post- 
transcriptionally on the bicoid protein (Bed) to 
repress its action in the terminal region. This 
leads to the expression of the head gap genes as 
an anterior stripe, responsible for development 
of a specific head region. While bicoid is setting 
up their posterior margin, the torso group, pre- 
venting activation by bicoid, sets up their ante- 
rior margin. 
We recently identified a gene that has such an 
expression pattern and encodes a homeodomain 
with a DNA-binding specificity related to that of 
Bed. We are investigating the control of the new 
gene's pattern of expression, and are analyzing 
phenotypes in the head region for genetic dele- 
tions of the locus. 
The demonstration of a direct interaction be- 
tween bicoid and the maternal torso group is the 
first clue for understanding the formation of head 
structure. It also presents us with a unique oppor- 
tunity to use a combination of biochemical and 
genetic approaches to address the nature and reg- 
ulation of the post-transcriptional modifications 
of a transcription factor in the context of a devel- 
oping organism. 
Regulation of the Segmentation Gene hb 
Molecular dissection of the hb promoter by sev- 
eral groups has allowed definition of the sites of 
action of bed. Our in vivo studies have uncov- 
ered a more complex regulation of hb. As de- 
scribed above, hb appears to be involved in the 
establishment of its own early expression, in syn- 
ergy with bed. We have identified in vitro, in the 
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