Morphogen Gradients and the Control of Body Pattern in Drosophila 
the bed morphogen in directly activating a num- 
ber of subordinate signaling molecules in spe- 
cific domains of the early embryo. However, we 
have recently conducted experiments showing 
that this view is incorrect and have provided evi- 
denceu that nos functions only to ensure the 
graded expression of another morphogen — sur- 
prisingly, the hb protein. 
As discussed above, graded bed protein di- 
rectly activates transcription of the hb gene in a 
broad anterior domain of the embryo. The hb 
gene, however, is also transcribed maternally: 
upon fertilization, maternal hb transcripts situ- 
ated in the posterior half of the embryo appear to 
be blocked translationally and subsequently de- 
stabilized by localized nos activity. Thus, like 
bed, nos also generates differential hb protein 
expression along the anteroposterior axis, albeit 
by a different molecular mechanism. 
Differential hb activity, whether generated 
under the control of the bed or nos determinants, 
appears to be involved in specifying most of the 
posterior body pattern. To test whether hb pro- 
tein functions as the primary gradient morphogen 
organizing the posterior body pattern, a series of 
mutant embryos have been generated that lack 
both the anterior (bed} and terminal (tor) mor- 
phogen systems, but retain the posterior system 
(nos) and maternal hb transcripts derived from 0 
to 4 copies of the hb gene. Under these circum- 
stances, the formation of posterior body pattern is 
solely dependent on the graded distribution of hb 
protein derived from maternal transcripts. More- 
over, different threshold concentrations of hb 
protein can be shown to determine distinct 
boundaries of expression of subordinate regula- 
tory molecules, most notably the gap gene pro- 
teins Kriippel (Kr) , knirps (knf) , and giant (gt) , 
which specify the position and polarity of most of 
the abdominal segments. 
These experiments indicate that posterior body 
pattern is established under the control of an hb 
morphogen gradient, much as anterior body pat- 
tern is controlled by the bed gradient. Since the 
bed gradient can itself create an hb protein gra- 
dient by its direct and localized effect on hb tran- 
scription, it has the capacity in principle to spec- 
ify virtually the entire body pattern. These 
findings reveal a basic asymmetry in the control 
of the anteroposterior body plan and provide an 
indication of how a relatively simple morphogen 
gradient like bed can generate a more elaborate 
and long-ranging system of spatial cues. 
Control of Terminal Body Pattern 
by the tor Receptor 
Recent studies in other laboratories have estab- 
lished the existence of a third primary determi- 
nant system that distinguishes end portions of the 
body pattern from the middle. A critical determi- 
nant in this system appears to be a receptor tyro- 
sine kinase encoded by the tor gene. In studies 
performed in this laboratory, the tor protein has 
been shown to be expressed uniformly along the 
surface of early embryos, even though genetic ex- 
periments indicate that it must normally be active 
at both poles but inactive in the middle portion 
of the body. Hence the tor kinase, as anticipated 
from its deduced molecular structure, appears to 
function as a ubiquitous surface receptor that is 
activated only in the vicinity of the poles. 
Additional genetic and immunohistochemical 
experiments have confirmed this conclusion and 
suggested that tor is activated by a localized 11- 
gand initially tethered to the extracellular matrix 
surrounding the embryo. Finally, using a muta- 
tion of the tor gene that causes temperature- 
sensitive constitutive activity of the receptor, dif- 
ferent levels of tor activity have been shown to 
specify distinct portions of the terminal pattern. 
Thus polarized activity of the tor kinase at the 
surface of the embryo may specify terminal pat- 
tern by generating one or more gradients of intra- 
cellular signaling molecules — perhaps phos- 
phorylated substrates of the protein. The 
specification of terminal pattern may therefore 
differ from that of anterior and posterior pattern 
only in the mechanism by which graded expres- 
sion of the active morphogen is generated. 
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