segmentation genes and of genes in the nervous sys- 
tem. This is achieved by testing the ability of ver- 
sions of the prd gene, modified in regions encoding 
each of the subdomains of the Prd protein, to rescue 
some of the differential molecular phenotypes of 
prd~ embryos. 
From Segmentation to Organogenesis 
BK27 is a gene highly homologous to prd but 
which appears to be involved in the early steps of 
organogenesis. This gene is first expressed in a 
group of cells that represent the progenitor of the 
salivary gland placode, at a stage when no tissue dif- 
ferentiation has occurred. This expression is con- 
trolled by positional cues from the dorsoventral and 
anteroposterior determinants. As the expression of 
this gene precedes morphological events, it pro- 
vides a model of transcriptional commitment to a 
particular differentiation pathway. Presently mu- 
tants are being generated in this gene to analyze the 
expression of putative target genes and the resulting 
morphological phenotype. 
Because the protein encoded by BK27 hsis an orga- 
nization very similar to that of Prd but has a Prd 
domain from a divergent class, its product will also 
be very useful in dissecting the residues that deter- 
mine the specificity of the Prd domain. 
Down-regulation of the Morphogen Bicoid 
by the Torso Receptor-mediated 
Signal Transduction Cascade 
Most aspects of anterior body pattern are specified 
by a graded distribution of the Bicoid protein (Bed) , 
which is presumed to bind with different affinities 
to subordinate regulatory genes, leading to their 
transcriptional activation in distinct anterior do- 
mains. However, transcription of these target genes 
is subsequently repressed at the anterior pole in re- 
sponse to the local activation of the receptor tyro- 
sine kinase torso (tor) . Both activation by bed and 
repression by tor can be reproduced with an artifi- 
cial promoter consisting solely of bed-binding sites 
placed upstream of a naive transcriptional start site. 
Repression depends critically on the function of 
the Drosophila homologue of the serine-threonine 
kinase ra/(D-raf), but not on the two transcription 
factors whose local activity was previously thought 
to constitute the sole transcriptional effect of the tor 
signaling system. Thus the activity of Bed protein 
appears to be down-regulated by input from the tor 
signaling cascade, possibly by D-raf-dependent 
phosphorylation of the structural domain normally 
required for activating transcription. 
Applications to the National Institutes of Health 
and the American Cancer Society are pending for 
support of this part of the research program. 
Autoregulation of hunchback 
The expression of bed targets was previously 
thought to depend on Bed alone. However, the prod- 
uct of another maternal gene, hunchback (hb), ap- 
pears to be required for full synergistic activation 
with bed. An Hb protein binding site exists in close 
association with a Bed site in the zygotic hb pro- 
moter and may be required for hb activation. The 
contribution of the maternal component of hb to 
anterior patterning has implications for the evolu- 
tion of bed and hb morphogenetic functions. A clus- 
ter of Hb binding sites also exists in another region 
of the hb promoter that controls hb autoregulation 
at a later stage in development. 
Applications to the National Institutes of Health 
and the American Cancer Society are pending for 
support of this part of the research program. 
These studies have led Dr. Desplan and his col- 
leagues to investigate both the general transcrip- 
tional functions carried out by specific developmen- 
tal proteins and the particular properties of each 
gene product. The combinatorial effects of such fac- 
tors both in vitro and in vivo is now being investi- 
gated to acquire insight into the mechanisms con- 
trolling the coordinate expression of developmental 
genes. 
Dr. Desplan is also Associate Professor and 
Head of the Laboratory of Molecular Genetics at 
the Rockefeller University. 
Article 
Treisman, J., Harris, E., Wilson, D., and Desplan, 
C. 1992. The homeodomain: a new face for the 
helix-turn-helix? Bioessays 14:145-150. 
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