image. Thus, by swapping the 3'-UTR, nanos mRNA 
is mislocalized to the anterior pole and the Nanos 
protein gradient is set up at both ends of the embryo 
(because the mutant flies also carry the normal 
nanos gene), resulting in two complete abdomens. 
This experiment proved that a local source of the 
Nanos protein can establish polarity in the embryo. 
(This project is supported by a grant from the Na- 
tional Institutes of Health.) 
Germline Determination 
The other major interest of Dr. Lehmann and her 
associates is the origin of germ cells. The re- 
searchers want to know how germline tissues be- 
come different from other tissues. All animal species 
have some mechanism for setting aside germ cell 
precursors early in embryogenesis. Somehow these 
cells are protected from the signals that induce 
other cells to enter specific developmental path- 
ways; thus they retain the ability to contribute to the 
generation of an entirely new organism. 
At least eight genes (oskar, staufen, cappuccino, 
spire, mago nashi, vasa, valois, and tudor) are 
required for the localization of both the abdom- 
inal signal encoded by the nanos gene and a yet- 
unidentified signal that specifies the germ cell fate 
at the posterior pole. Molecular analysis indicates 
that the products of these genes act in a stepwise 
fashion to promote posterior pole plasm assembly. 
The Lehmann group and others have worked out the 
order of these steps; for example, the staufen gene 
product is required for localization of the oskar 
gene product, and both in turn are required for lo- 
calization of the vasa gene product to the posterior 
pole. This pathway can be summarized as follows: 
cappuccino, 
spire — ► staufen — ► oskar — ► 
» abdomen 
nanos 
vasa — ► tudor ^ 
germ cells 
The same mix-and-match strategy described for 
nanos has allowed Dr. Anne Ephrussi to test this 
stepwise assembly model. Here the target gene was 
oskar, which acts in the middle of the pole plasm 
pathway. Dr. Ephrussi identified the oskar RNA lo- 
calization signal within the 3'-UTR of oskar and re- 
placed it with that of bicoid. Insertion of this chi- 
meric gene into flies results in females that produce 
embryos with functional germ cells at both ends. 
Mislocalization of Oskar also leads to mislocaliza- 
tion of the abdominal signal nanos to the anterior. 
As a consequence these embryos form two opposing 
gradients of Nanos protein and develop two abdo- 
mens in mirror image. 
A genetic analysis further shows that ectopic germ 
cell formation and anterior localization of nanos 
RNA require the activity of oskar, vasa, and tudor, 
while other genes, like staufen, cappuccino, spire, 
valois, and mago nashi, are not required. Thus 
these latter genes fulfill accessory functions for lo- 
calizing the products of genes such as oskar to the 
posterior pole or for maintaining a functional germ 
plasm at this pole. These experiments have 
narrowed the number of genes directly involved in 
germ cell determination. Nevertheless the primary 
signal for germ cell determination still awaits iden- 
tification. (This project is supported by the National 
Institutes of Health and the Packard Foundation.) 
Dr. Lehmann is also Associate Member of the 
Whitehead Institute of Biomedical Research, Asso- 
ciate Professor of Biology at the Massachusetts In- 
stitute of Technology, and Adjunct Assistant Ge- 
neticist (Medicine) and Assistant Molecular 
Biologist at Massachusetts General Hospital, 
Boston. 
Articles 
Ephrussi, A., and Lehmann, R. 1992. Induction of 
germ-cell formation by oskar. Nature 358:387- 
392. 
Fischer-Vize, J.A., Vize, P.D., and Rubin, G.M. 
1992. A unique mutation in the Enhancer of split 
gene complex affects the fates of the mystery cells 
in the developing Drosophila eye. Development 
115:89-101. 
Lehmann, R. 1992. Germ-plasm formation and 
germ-cell determination in Drosophila. Curr 
Opin Genet Dev 2:543-549. 
90 
