with En-^^ will be analyzed, as well as expression 
of the three Gli genes in the postnatal cerebellum. 
Two approaches have been taken, in collabora- 
tion with Dr. Andrew McMahon (Roche Institute), 
to analyze possible interactions of the En and Wnt 
genes. One approach is to analyze the expression of 
the En genes in embryos mutant for Wnt-1. These 
studies have shown that, as in the fly, the En genes 
do not require Wnt-1 to be activated, but may re- 
quire Wnt- 1 for maintenance of En expression. The 
second approach has been to make double mutants 
and analyze the cerebellar phenotype. 
The Mouse Mash Genes 
A number of genes critical for development of the 
nervous system in Drosophila have been identified. 
The achaete-scute complex (AS-C) family of genes 
is required both for determination of neuroblasts 
from ectoderm and for specific differentiation of 
certain sensory neurons. These genes are all thought 
to be transcription factors that dimerize and bind 
DNA through a basic helix-loop-helix (bHLH) pro- 
tein motif. To determine whether these genes play a 
similar role in development of the mammalian ner- 
vous system. Dr. Joyner and her colleagues cloned 
two mouse genes, Mash-1 and -2 (Mash: mamma- 
lian achaete-scute homologue), that contain an AS- 
C type of bHLH domain, based on their homology to 
the Drosophila hS-C genes, and Dr. David Anderson 
and his colleagues (HHMI, California Institute of 
Technology) cloned two Mash genes of the rat. 
Mash- 1 is expressed primarily in proliferating cells 
of the embryonic nervous system, whereas Mash-2 
expression is restricted to proliferating cells of the 
trophectoderm extraembryonic lineage. Mice het- 
erozygous for a targeted deletion of Mash-1 have 
been made and will be bred to determine whether 
Mash-1 is essential for development of the nervous 
system. 
Dr. Joyner is a Senior Scientist at the Samuel 
Lunenfeld Research Institute of Mount Sinai Hos- 
pital, Toronto, Associate Professor of Molecular 
and Medical Genetics at the University of 
Toronto, and a Medical Research Council of Can- 
ada Scholar. 
Books and Chapters of Books 
Sedivy, J.M., and Joyner, A.L. 1992. Gene Target- 
ing. New York: Freeman. 
Articles 
Joyner, A.L. 1991. Gene targeting and gene trap 
screens using embryonic stem cells: new ap- 
proaches to mammalian development. Bioessays 
13:649-656. 
Joyner, A.L., and Hanks, M. 1991. The engrailed 
genes: evolution of function. Semin Dev Biol 
2:435-445. 
McMahon, A.P., Joyner, A.L., Bradley, A., and 
McMahon, J.A. 1992. The midbrain-hindbrain 
phenotype of Wnt- 1~ /Wnt- 1~ mice results from 
stepwise deletion of e«^ra«7e<^-expressing cells 
by 9.5 days postcoitum. Cell 69:581-595. 
Moens, C.B., Auerbach, A.B., Conlon, R.A., Joyner, 
A.L., and Rossant, J. 1992. A targeted mutation 
reveals a role for N-mjc in branching morphogen- 
esis in the embryonic mouse lung. Genes Dev 
6:691-704. 
Skarnes, W.C., Auerbach, B.A., and Joyner, A.L. 
1992. A gene trap approach in mouse embryonic 
stem cells: the /acZ reporter is activated via splic- 
ing, reflects endogenous gene expression, and is 
mutagenic in mice. Genes Dev 6:903-918. 
PRACTICAL APPLICATIONS OF REPLICATABLE RNAs AND RNA ENZYMES 
IN THE DIAGNOSIS OF INFECTIOUS DISEASES 
PaulM. Lizardi, Ph.D., International Research Scholar 
Epidemiological monitoring of infectious dis- 
eases is a high priority in developing countries. The 
list of diseases producing significant mortality and 
morbidity includes AIDS, malaria, amebiasis, tuber- 
culosis, hepatitis, trypanosomiasis, typhoid fever, 
diverse intestinal infections, and recently cholera. 
There is a need for techniques that will permit the 
rapid and reliable detection of infectious agents, so 
that epidemiological monitoring and patient man- 
agement can be more effective. The use of the poly- 
merase chain reaction (PGR) for the detection of 
pathogens has demonstrated the power of nucleic 
acid amplification as a diagnostic tool. Hence there 
is considerable interest in exploring other nucleic 
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