Anterior-Posterior Patterning in the Early Mammalian Embryo 
ration with Alexandra Joyner (HHMI, Interna- 
tional Research Scholar), we are using gene-trap 
vectors inserted into embryonic stem (ES) cells as 
one strategy for identifying expression domains. 
In these vectors the bacterial lacZ gene lacks a 
promoter but has a splice acceptor sequence up- 
stream, such that /«cZ can be activated as a fusion 
transcript when the vector inserts in the intron of 
an active host gene. Many /acZ-expressing ES 
clones with different integrations are being as- 
sessed in chimeras for their pattern of expression 
at gastrulation. We have screened more than 200 
such lines to date and find about 20 percent with 
spatially restricted expression patterns. The 
screen will continue, and the most interesting 
lines will be cloned from the fusion transcript 
and taken through the germline to analyze the 
mutant phenotype induced by the vector 
integration. 
Other more rapid screens for expression pat- 
terns using whole-mount in situ hybridization 
with cDNA clones are in the pilot stages. The com- 
bination of large-scale searches for new patterns 
of gene expression with embryonic manipulation 
experiments using such genes as markers should 
give new insights into the basis of patterning in 
the mouse embryo. This broad approach does 
not, of course, eliminate the need to study further 
the role of specific genes already identified as 
potential regulators of development, and we are 
also undertaking the targeted mutagenesis of a 
number of such genes. 
Mouse embryos at day 8.5, showing expression domains of 
RAREhsplacZ (top), Hox-2.9 (middle), andKxox-20 (bottom). 
Research and photograph by Ron Conlon in the laboratory of 
fanet Rossant. 
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