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members of the eye specification cascade, in addition to their
roles in eye specification, are expressed and regulate the
development of several tissues. The retinal determination
gene dachshund (dac) is no exception. In
fact it might be one of the more dynamically expressed members
of the network. DAC protein is distributed within the developing
embryonic head, central nervous system and several imaginal
discs that give rise to the antennae, legs, wings and genitals
(Figure 1).
We
have previously demonstrated that the TGF? signaling cascade
and the transcription factor zerknullt (zen)
negatively regulate dac expression within the embryonic head.
In loss-of-function mutants dac is ectopically expressed
within the visual primordium (Figure 2). The ZEN protein is
characterized by the presence of the homeodomain (HD), which
is a structural motif for DNA binding and is involved in several
patterning decisions during embryogenesis. The zen gene lies
within the Antennapedia Hox gene cluster but is not considered
to be a true Hox gene in Drosophila. Genes that lie
within this genomic region arose through a series of ancient
duplication events and thus there is considerable sequence
conservation between the HDs of zen and members of
the Antennapedia Hox gene cluster. Additionally, the HDs of
zen and members of the Bithorax complex also share considerable
sequence similarity. Interestingly, one member of the Antennapedia
complex, proboscipedia (pb), has been shown
by others to regulate the expression of dachshund.
We
have set out to examine the role that may be played by the
other Hox genes (labial, proboscipedia,
Sex combs reduced, Deformed, Antennapedia,
Ultrabithorax, abdominal-A and abdominal-B)
in regulating dachshund transcription. The possibility
that dac may be regulated by these genes during development
is raised by the fact that (1) the Hox genes are expressed
in regions of the embryo that express dac and (2)
both zen and pb regulate DAC protein distribution.
In order to approach this question we first expressed each
of the Hox genes within the developing embryo and imaginal
discs and assayed the effect on DAC protein distribution.
One of the more exciting results is that forced expression
of Deformed (Dfd) is sufficient to induce
the expression of dachshund within the developing
wing. We are extending these observations by creating a series
of chimeric proteins (between zen and Dfd)
that will determine if the ability of Dfd to induce
dac expression is contained solely within the HD, solely within
part of the N and/or C terminal regions or if a combination
of domains is required (Figure 3). A similar analysis if being
conducted on several other Hox genes that have shown interesting
patterns of regulating dac expression.
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