Function of Proto-oncogenes in Early Embryogenesis 
control cell-cell interactions. The wingless gene 
is a good example, encoding a secreted factor, 
but other segment polarity genes are thought to 
interact with wingless. To study the properties of 
the wingless protein, we have made antibodies 
that recognize the protein in whole-mount em- 
bryos and in individual cells. 
The protein is seen on the surface of cells and 
in intracellular structures that constitute uptake 
vesicles. Such structures are also seen in cells ad- 
jacent to those that make the wingless protein, 
suggesting a paracrine mechanism of action of 
the gene. When we now look at the distribution 
of the wingless protein in embryos that are mu- 
tant for some other segment polarity genes, we 
can observe differences suggesting that wingless 
interacts directly with the products of these 
genes. 
In other experiments, we have overexpressed 
the wingless gene from a heat-shock promoter 
and transfected it into established Drosophila 
cell lines. By deliberately altering the expression 
of the gene in whole embryos or in cultured cells, 
we are identifying additional genes that are in- 
volved in the wingless signal transduction path- 
way. For example, our finding that misexpression 
of wingless in an embryo results in large areas of 
pattern abnormalities can be taken as evidence 
that many, if not all, cells can receive the wing- 
less signal and must therefore have receptors. 
We have also found that wingless in Drosoph- 
ila is also part of a gene family, with at least two 
additional members. These genes, called \)Wnt-2 
and DWnt-5 for the time being, are also ex- 
pressed during early embryogenesis, but in char- 
acteristic patterns that differ from wingless. 
In the analysis of the mechanism of action of 
the Wnt genes in mouse development, we hope 
to take advantage of the results of the Drosophila 
work, conceivably by isolating the mouse homo- 
logues of those fly genes that have been shown to 
interact with wingless. 
328 
