Genetic Control of Pattern Formation and 
Germline Determination in Drosophila 
Ruth Lehmann, Ph.D. — Assistant Investigator 
Dr. Lehmann is also Associate Member of the Whitehead Institute of Biomedical Research, Assistant Pro- 
fessor of Biology at the Massachusetts Institute of Technology, and Assistant Molecular Biologist at the 
Massachusetts General Hospital, Boston. She received her M.Sc. degree from the University of Freiburg, 
where she worked with J. Campos-Ortega on early neurogenesis in Drosophila. She received her Ph.D. de- 
gree from the University of Tiibingen, where she worked with Christiane Niisslein-Volhard on the genetics 
of pattern formation in the Drosophila embryo. After postdoctoral training in Tiibingen and at the MRC 
in Cambridge with Michael Wilcox, she joined the Whitehead Institute. 
OUR laboratory is interested in the genetic 
mechanisms that control the establishment 
of polarity during embryogenesis. In Drosophila, 
basic information about the "coordinates" of the 
embryo is supplied to the egg cell during its matu- 
ration in the mother. Mutations in maternal genes 
have led to the identification of a small number of 
genes that are required for the establishment of 
dorsal-ventral and anterior-posterior polarity in 
the embryo. In these mutants the lack of a partic- 
ular maternal gene product leads to a lethal phe- 
notype in the embryo. 
Three independent morphogenetic systems are 
required for the establishment of pattern along 
the anterior-posterior axis. The anterior system 
controls the development of head and thorax, the 
posterior system determines the abdominal re- 
gion, and the terminal system is required for the 
most anterior and posterior structures. The ante- 
rior and posterior systems act through factors that 
are localized to the respective poles. For the ante- 
rior group of genes, the localized factor is the 
mRNA product of the gene bicoid. The other ante- 
rior genes are involved in the localization of bi- 
coid RNA. Localization of the bicoid RNA is neces- 
sary for the formation of a concentration gradient 
of bicoid protein. This gradient along the ante- 
rior-posterior axis determines thresholds for the 
expression of zygotic target genes. Thus high lev- 
els of bicoid promote head formation, while 
lower levels promote thorax formation. 
We have concentrated on dissecting the path- 
way that leads to normal development of the pos- 
terior region of the embryo. Nine maternal genes 
have been identified that set the basic posterior 
pattern. These genes, referred to as the posterior 
group, share the abdominal phenotype: homozy- 
gous mutant females produce offspring that lack 
abdominal segmentation. Only the nanos gene, 
however, encodes the localized signal required 
for the development of the abdomen, while seven 
genes — oskar, vasa, tudor, valois, staufen, 
cappuccino, and spire — are required for the lo- 
calization of nanos. 
These genes, in addition to the abdominal phe- 
notype, show an effect on germ cell formation: 
mutant embryos do not form a specialized poste- 
rior pole plasm that normally contains the polar 
granules, and hence these embryos lack pole 
cells, the precursors of the germline cells in Dro- 
sophila. One gene, pumilio, is required for the 
distribution of the nanos protein. Our molecular 
analysis of the posterior group is aimed at deter- 
mining how nanos and various other RNA species 
become localized to the posterior pole and how 
the pole plasm, composed of RNA and protein, is 
assembled. 
Synthesis and Function of the 
Abdominal Signal 
Through genetic experiments as well as cyto- 
plasmic transfers between wild-type and mutant 
embryos, we concluded that the specialized cyto- 
plasmic zone at the posterior pole is the source of 
an abdominal signal and that embryos derived 
from females mutant for any one of the posterior 
group genes lack a common signal in the abdomi- 
nal region. Depending on the gene affected, mu- 
tant embryos are deficient in the synthesis, stor- 
age, or transport of the signal. 
The gene nanos is central to the genetic path- 
way leading to abdomen formation. We have iso- 
lated and cloned the gene and have shown that it 
encodes the posterior signal. During oogenesis, 
nanos mRNA is transcribed and becomes local- 
ized to the posterior pole of the oocyte. The cen- 
tral role of nanos for posterior pattern formation 
is demonstrated by the finding that nanos tran- 
script synthesized in vitro from a nanos cDNA 
rescues the abdominal segmentation phenotype 
not only of nanos mutant embryos but also of all 
posterior group mutants so far tested. Since seven 
of the nine mutants (except nanos and pumilio) 
also lack pole plasm and fail to localize nanos 
RNA, we can conclude that in pole plasm-defec- 
tive mutants the abdominal segmentation defect 
is a consequence of a lack of localized nanos ac- 
tivity ■ In future experiments we will determine 
cis-acting sequences within the nanos mRNA, 
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