Hsiao, shown that fibroblast cell lines derived from 
neonatal A'^/a animals exhibit a remarkably high 
degree of spontaneous transformation in cell cul- 
ture compared with congenic a/a animals. The 
transformed cells form foci in monolayer cultures, 
exhibit anchorage independence, and form tumors 
when injected into nude mice. In addition, trans- 
formed cells derived from A'^/a fibroblasts always 
contain restriction fragment length variants (RFLVs) 
associated with the ^'^-containing chromosome but 
occasionally lose RFLVs associated with the 
fl-containing chromosome. Furthermore, transfec- 
tion of a/a fibroblasts with DNA from A"^/— fibro- 
blasts confers the phenotype of increased spontane- 
ous transformation, which suggests this is a 
dominant trait that may be analogous to the in- 
creased tumor susceptibility observed in A^/— or 
animals in vivo. Expression of the 900-bp 
cDNA in a/a fibroblasts will help to determine 
whether the pleiotropic effects of A^ (and A'^) are 
mediated by a single transcriptional unit. 
Dr. Barsh is also Assistant Professor of Pediat- 
rics at the Stanford University School of Medicine. 
Articles 
Link, R., Daunt, D., Barsh, G., Chruscinski, A., and 
Kobilka, B.K. 1992. Cloning of two mouse genes 
encoding a2-^dve^nevgic receptor subtypes and 
identification of a single amino acid in the mouse 
a2-C10 homolog responsible for an interspecies 
variation in antagonist binding. Mol Pharmacol 
42:16-27. 
OUmann, M.M., Winkes, B.M., and Barsh, G.S. 
1992. Construction, analysis, and application of a 
radiation hybrid mapping panel surrounding the 
mouse agouti \oc\is. Genomics 13:731-740. 
GENETIC CONTROL OF SEGMENTAL DIFFERENTIATION 
Philip A. Beachy, Ph.D., Assistant Investigator 
The ontogeny of many animal groups entails sub- 
division of the embryo into a series of homologous 
segments to be differentiated along distinct path- 
ways. These processes are best understood in Dro- 
sophila, where they are controlled by a temporally 
and spatially ordered hierarchy of gene expression. 
The work in Dr. Beachy's laboratory centers upon 
the two groups of genes within this hierarchy that 
are most directly concerned with control of seg- 
mental differentiation. The segment polarity group 
specifies the positional identities of cells within a 
segment, and the homeotic group specifies the dis- 
tinct identities of individual segments. Both are re- 
quired to produce the diverse array of segmentally 
specialized structures characteristic of the Drosoph- 
ila larva and adult. 
Identification of a New Signaling Molecule 
Required for Positional Identity 
During the syncytial period of early Drosophila 
embryogenesis, morphogens (primarily transcrip- 
tional regulatory proteins) can exert effects upon 
gene expression in distant nuclei by diffusion from 
the sites at which they are synthesized. This form of 
position-dependent communication is required to 
coordinate subdivision of the embryo into broad 
zones and eventually into segments. Following the 
syncytial stage, further signaling activity functions 
to specify and refine the positional identities of cells 
within a segment. At this stage, however, signaling 
mechanisms must reckon with the presence of cell 
membranes. 
Positional identities of cells within a segment are 
the province of the segment polarity genes. John 
Lee, Doris P. von Kessler, and Dr. Suki Parks have 
isolated and characterized at the molecular level a 
segment polarity gene whose mutant phenotype was 
first reported 1 2 years ago. This gene, named hedge- 
hog (hh) for the continuous pattern of bristles ob- 
served on the ventral surface of mutant larvae, is 
required to maintain the positional identities of 
cells to either side of the parasegment boundary. 
This boundary marks an important cell lineage re- 
striction and functions as a frame of reference for 
later expression of homeotic genes. Long before any 
overt morphological differentiation, the boundary 
is defined by the expression of the segment polarity 
genes wingless (wg) in a stripe of cells to the ante- 
rior of the boundary and engrailed (en) in a neigh- 
boring stripe of cells to the posterior. The en and wg 
genes are mutually required for maintenance of the 
other's expression; their expression in different 
150 
