that they might conserve potential heterodimeric 
functions. The Evans laboratory has recently demon- 
strated that usp can substitute for RXR in stimulat- 
ing binding of the RAR, TR, and VDR to target DNA. 
These observations led to the search for and ulti- 
mate identification of the ecdysone receptor (EcR) 
as a Drosophila partner of usp. Together, usp and 
EcR bind DNA in a highly cooperative fashion. Co- 
transfection of both EcR and usp expression vectors 
is required to render cultured mammalian cells ec- 
dysone responsive. These results indicate that usp is 
an integral component of the functional EcR. By 
demonstrating that receptor heterodimer formation 
precedes the divergence of vertebrate and inverte- 
brate lineages, these data underscore a central role 
for RXR and its homologue usp in the evolution and 
control of the nuclear receptor-based endocrine 
system. 
Dr. Evans is also Professor at the Salk Institute 
for Biological Studies and Adjunct Professor of Bi- 
ology and of Biomedical Sciences at the University 
of California, San Diego. 
Articles 
Blumberg, B., Mangelsdorf, D.J., Dyck, J.A., Bittner, 
D.A., Evans, R.M., and De Robertis, E.M. 1992. 
Multiple retinoid-responsive receptors in a single 
cell: families of retinoid "X" receptors and reti- 
noic acid receptors in the Xenopus egg. Proc Natl 
Acad Sci USA 89:2321-2325. 
Borrelli, E., Sawchenko, P.E., and Evans, R.M. 
1991. Pituitary hyperplasia induced by ectopic 
expression of nerve growth factor. Proc Natl 
Acad Sci USA 89:2764-2768. 
Cadepond, F., Gasc, J.-M., Delahaye, F., Jibard, N., 
Schweizer-Groyer, G., Segard-Maurel, I., Evans, 
R.M., and Baulieu, E.-E. 1992. Hormonal regula- 
tion of the nuclear localization signals of the hu- 
man glucocorticosteroid receptor. Exp Cell Res 
201:1718-1727. 
Heyman, R.A., Mangelsdorf, D.J., Dyck, J.A., Stein, 
R.B., Eichele, G., Evans, R.M., and Thaller, C. 
1992. 9-cis retinoic acid is a high affinity ligand 
for the retinoid X receptor. Cell 68:397-406. 
Kakizuka, A., Sebastian, B., Borgmeyer, U., Hermans- 
Borgmeyer, I., Bolado, J., Hunter, T., Hoekstra, 
M.F., and Evans, R.M. 1992. A mouse cdc25 ho- 
molog is differentially and developmental ly ex- 
pressed. Genes Dev ():'^lS-590. 
Kitabayashi, I., Kawakami, Z., Chiu, R., Ozawa, K., 
Matsuoka, T., Toyoshima, S., Umesono, K., 
Evans, R.M., Gachelin, G., and Yokoyama, K. 
1992. Transcriptional regulation of the c-jun 
gene by retinoic acid and El A during differentia- 
tion of F9 cells. EMBO / 11:167-175. 
Kliewer, S.A., Umesono, K., Heyman, R.A., Man- 
gelsdorf, D.J., Dyck, J.A., and Evans, R.M. 1992. 
Retinoid X receptor-COUP-TF interactions modu- 
late retinoic acid signaling. Proc Natl Acad Sci 
USA 89:1448-1452. 
Kliewer, S.A., Umesono, K., Mangelsdorf, D.J., and 
Evans, R.M. 1992. The retinoid X receptor inter- 
acts with nuclear receptors in retinoic acid, thy- 
roid hormone and vitamin D3 signalling. Nature 
355:446-449. 
Mangelsdorf, D.J., Borgmeyer, U., Heyman, R.A., 
Zhou, J.Y., Ong, E.S., Oro, A.E., Kakizuka, A., and 
Evans, R.M. 1992. Characterization of the three 
RXR genes that mediate the action of 9-cis reti- 
noic acid. Genes Dev 6:329-344. 
Miller, W.H., Jr., Kakizuka, A., Frankel, S.R., 
Warrell, R.P., Jr., DeBlasio, A., Levine, K., Evans, 
R.M., and Dmitrovsky, E. 1992. Reverse tran- 
scription polymerase chain reaction for the 
rearranged retinoic acid receptor a clarifies diag- 
nosis and detects minimal residual disease in 
acute promyelocytic leukemia. Proc Natl Acad 
Sci USA 89:2694-2698. 
Oro, A.E., McKeown, M., and Evans, R.M. 1992. 
The Drosophila nuclear receptors: new insight 
into the actions of nuclear receptors in develop- 
ment. Curr Opin Genet Dev 2:269-274. 
Oro, A.E., McKeown, M., and Evans, R.M. 1992. 
The Drosophila retinoid X receptor homolog ul- 
traspiracle functions in both female reproduc- 
tion and eye morphogenesis. Development 
115:449-462. 
NEUROSCIENCE 399 
