gene activation. In these experiments they will alter 
the expression levels or domains of expression of 
segment polarity genes that have been speculated to 
act as signaling molecules {wingless, hedgehog), 
receptors (patch), and transcription factors {Cubi- 
^^^interruptus ^ goQseberry) . These experiments will 
allow them to test the epistatic relationship be- 
tween the various segment polarity genes. 
Dr. Perrimon is also Assistant Professor of Ge- 
netics at Harvard Medical School. 
Articles 
Chou, T.B., and Perrimon, N. 1 992. Use of a yeast 
site-specific recombinase to produce female 
germline chimeras in Drosophila. Genetics 
131:643-653. 
Eberl, D.F., Perkins, L.A., Engelstein, M., Hilliker, 
A.J., and Perrimon, N. 1992. Genetic and devel- 
opmental analysis of polytene section 1 7 of the X 
chromosome of Drosophila melanogaster. Ge- 
netics 130:569-583. 
Kassis, J. A., Noll, E., VanSickle, E.P., Odenwald, 
W.F., and Perrimon, N. 1992. Altering the inser- 
tional specificity of a Drosophila transposable el- 
ement. Proc Natl Acad Sci USA 89:1919-1923. 
Perkins, L.A., Larsen, I., and Perrimon, N. 1992. 
corkscrew encodes a putative protein tyrosine 
phosphatase that functions to transduce the termi- 
nal signal from the receptor tyrosine kinase torso. 
Ce// 70:225-236. 
Perkins, L.A., and Perrimon, N. 1991 ■ The molecu- 
lar genetics of tail development in Drosophila 
melanogaster. In Vivo 5:521-531. 
Rutledge, B.J., Zhang, K., Bier, E., Jan, Y.N., and 
Perrimon, N. 1992. The Drosophila spitz gene 
encodes a putative EGF-like growth factor in- 
volved in dorsal-ventral axis formation and neuro- 
genesis. Genes Dev 6:\5Qi-l5\l . 
Wieschaus, E., Perrimon, N., and Finkelstein, R. 
1992. orthodenticle activity is required for the 
development of medial structures in the larval 
and adult epidermis of Drosophila. Development 
115:801-811. 
MOLECULAR GENETICS AND CHROMOSOME STRUCTURE 
Stephen T. Reeders, M.D., Associate Investigator 
The molecular genetics of inherited renal disease 
is the major focus of Dr. Reeders' laboratory. 
Autosomal Dominant Polycystic Kidney 
Disease (ADPKD) 
One of the most common human genetic diseases, 
ADPKD affects at least 1 in 1,000 adults. Current 
evidence suggests that hyperplasia of the renal tubu- 
lar epithelium leads to progressive dilatation of tu- 
bules and irreversible deterioration in renal func- 
tion; dialysis or transplantation are usually required. 
In addition, recent work suggests that in this disease 
several proteins normally found on the basolateral 
surface of the polarized epithelium are found on the 
apical surface in renal cysts. 
To understand the underlying genetic mechanism 
of ADPKD, Dr. Reeders and his colleagues are at- 
tempting to isolate PKDl, the common locus mu- 
tated in the disease. In addition, they have shown 
that a second locus, PKD2, is occasionally mutated, 
but that these mutations produce a milder form of 
the disease. Isolation of these genes is a prerequisite 
for the study of their protein products and of the 
way in which mutations disturb the functions of 
these products. 
The genomic region containing the PKDl gene 
lies in a 450-kb segment of chromosome 16, band 
pi 3.3 - This segment has been cloned into a series of 
overlapping cosmids. Twenty-three cDNAs have 
been isolated from the region. Most of these genes 
are housekeeping genes that are expressed in the 
kidney and most other tissues. Sequence analysis has 
shown that all of these genes are novel. They in- 
clude a gene encoding a zinc finger protein, a cyclin 
gene, a ras-like gene, and a gene whose product has 
similarities with 13 subunits of G-binding proteins. 
The laboratory is currently using single-strand con- 
formation analysis to screen these genes for disease- 
associated mutations and differences in chemical 
cleavage specificities. 
Dr. Reeders has also occasionally observed onset 
of ADPKD in neonates and young children. This sug- 
gests that the disease may be caused by an unstable 
repeat element similar to the ones found to cause 
the fragile X syndrome, myotonic dystrophy, and 
Kennedy syndrome. Several trimeric repeats have 
been identified from the region, and these are under 
investigation. (A grant from the National Institute of 
Diabetes and Digestive and Kidney Diseases sup- 
ported the work described above.) 
252 
