periments are under way in which MT-III expression 
will either be increased or eliminated, to help de- 
fine the function of this gene and its potential role in 
neural degenerative diseases such as Alzheimer's. 
Dr. Palmiter is also Professor of Biochemistry at 
the University of Washington, Seattle. 
Books and Chapters of Books 
Moriyama, T., Guilhot, S., Moss, B., Pinkert, C.A., 
Palmiter, R.D., Brinster, R.L., Klopchin, K., Kan- 
agawa, O., and Chisari, F.V. 1991- Hepatitis B 
surface antigen-specific antibody and T cell- 
mediated hepatocellular injury in hepatitis B 
virus transgenic mice. In Viral Hepatitis and 
Liver Disease (Hollinger, F.B., Lemon, S.M., and 
Margolis, H.S., Eds.). Baltimore, MD: Williams & 
Wilkins, pp 282-288. 
Articles 
Evans, J.P., and Palmiter, R.D. 1991- Retrotrans- 
position of a mouse LI element. Proc Natl Acad 
Sci USA 88:8792-8795. 
Kapur, R.P., Hoyle, G.W., Mercer, E.H., Brinster, 
R.L., and Palmiter, R.D. 1991. Some neuronal 
cell populations express human dopamine 
/3-hydroxylase-/acZ transgenes transiently during 
embryonic development. Neuron 1:1X1-121 . 
Mercer, E.H., Hoyle, G.W., Kapur, R.P., Brinster, 
R.L., and Palmiter, R.D. 1991. The dopamine 
i8-hydroxylase gene promoter directs expression 
of E. coli lacZ to sympathetic and other neurons 
in adult transgenic mice. Neuron 7:703-716. 
Messing, A., Behringer, R.R., Hammang, J.P., Pal- 
miter, R.D., Brinster, R.L., and Lemke, G. 1992. 
PO promoter directs expression of reporter and 
toxin genes to Schwann cells in transgenic mice. 
Neuron 8:507-520. 
Palmiter, R.D., Findley, S.D., Whitmore, T.E., and 
Durnam, D.M. 1992. MT-III, a brain-specific 
member of the metallothionein gene family. Proc 
Natl Acad Sci USA 89:6333-6337. 
Rexroad, C.E., Mayo, K., Bolt, D.J., Elsasser, T.H., 
Miller, K.F., Behringer, R.R., Palmiter, R.D., 
and Brinster, R.L. 1991. Transferrin- and albumin- 
directed expression of growth-related peptides in 
transgenic sheep. /^«/m 5c/ 69:2995-3004. 
GENETIC AND MOLECULAR DISSECTION OF SIGNAL TRANSDUCTION PATHWAYS 
NoRBERT Perrimon, Ph.D., Assistunt Investigator 
Although biochemical analyses of signal transduc- 
tion molecules have been important in demonstrat- 
ing functional capabilities, they have often failed to 
reveal how these molecules actually work in vivo. 
Many signal transduction components function pro- 
miscuously in in vitro assays, interacting with a 
broad spectrum of substrates. Applying the tools of 
genetics to establish the epistasis between proteins 
involved in signal transduction will establish the in 
vivo relationships between signal transducers. Dr. 
Perrimon and his colleagues have undertaken a mo- 
lecular genetic analysis of two signal transduction 
pathways implicated in cell fate determination in 
the Drosophila embryo. The long-term goal is to 
identify the components involved in these pathways 
and test their interactions, in order to decipher how 
a morphogenetic signal controls gene expression in 
the receiving cells. 
The Terminal Signal Transduction Pathway 
The establishment of cell fates along the anterior- 
posterior axis of the Drosophila embryo is under 
the control of three groups or systems of maternally 
expressed genes: the anterior, posterior, and termi- 
nal systems. Genetic analysis of the terminal system 
supports a model whereby localized activation of 
the torso receptor tyrosine kinase at the egg poles 
triggers a phosphorylation cascade that ultimately 
controls the expression of the tailless and hucke- 
bein transcription factors. Dr. Perrimon and his col- 
leagues have characterized two signal transducers of 
torso: D-raf the Drosophila homologue of the 
mammalian serine/threonine kinase Rafl, and 
corkscrew (csw) , which encodes a novel nonrecep- 
tor protein-tyrosine phosphatase containing two 
SH2 domains. Genetic experiments and studies of 
downstream gene expression in mutant embryos 
support a model in which D-raf is the signal trans- 
ducer of the membrane-bound receptor tyrosine 
kinase encoded by torso, while csw acts by up- 
regulating the activity of D-raf. In addition. Dr. 
Perrimon and his colleagues have recently shown 
that D-ras 1 operates upstream of D-raf to transduce 
the torso signal. 
Using in vivo functional assays. Dr. Perrimon and 
his colleagues have demonstrated that D-raf is the 
true Drosophila homologue of mammalian Rafl. 
Experiments are in progress to test whether the csw 
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