68
M. Affolter
5.1.2 HOX Genes and Positional Signaling: Is There a Link?
One transcriptional target of DPP-mediated endoderm induction is the
homeotic gene lab. To investigate the potential role of SCHNURRI in
regulating lab activation, we generated a large number of mutant versions of the DPP-dependent enhancer of lab, called lab550. Although
this analysis has not yet allowed us to draw any firm conclusions
concerning the function of SCHNURRI, we made a most interesting and
intriguing observation. We found that the activity of the enhancer is
stimulated significantly only by DPP signaling upon binding of the LAB
homeotic protein and its cofactor EXTRADENTICLE (EXD) to an
essential and evolutionarily conserved sequence element within the 5'
part of the enhancer (Grieder et al. 1997). Thus, the lab550 enhancer
appears to integrate positional information (via the region-specific expression of the home otic gene lab) and spatiotemporal information (via
DPP signaling); only when these inputs act in concert in an endodermal
cell is the enhancer fully active. These results illustrate how synergistic
effects on an enhancer carrying both DPP- and HOM-responsive sequences can contribute to the generation of a specific cellular response
to DPP; only cells expressing lab can activate this particular DPP-responsive enhancer efficiently.
When these results are interpreted with respect to the possible function of homeotic genes during development, it emerges that one of the
very important roles of homeotic proteins (which are the classic example of proteins conveying positional information to cells in a developing
embryo) is to participate in the interpretation of signaling inputs into
appropriate, position-specific transcriptional responses. Although regulatory cross-talk is a common occurrence in the control of gene transcription, there is little or no precedent for the interaction of homeotic
proteins with those involved in signaling, and I am not aware that such a
direct "signal interpretation" function of the homeotic proteins has been
proposed previously.
Such a proposal is very interesting for discussion in the context of the
developing midgut. As already mentioned, DPP not only induces the
expression of specific genes in the endodermal ceUlayer in the Drosophila embryo, but also in the VM cell layer itself. Genetic studies
provided evidence that the cellular transcriptional response to DPP in
the VM largely depends on the parasegmental provenance of, and thus
M. Affolter
5.1.2 HOX Genes and Positional Signaling: Is There a Link?
One transcriptional target of DPP-mediated endoderm induction is the
homeotic gene lab. To investigate the potential role of SCHNURRI in
regulating lab activation, we generated a large number of mutant versions of the DPP-dependent enhancer of lab, called lab550. Although
this analysis has not yet allowed us to draw any firm conclusions
concerning the function of SCHNURRI, we made a most interesting and
intriguing observation. We found that the activity of the enhancer is
stimulated significantly only by DPP signaling upon binding of the LAB
homeotic protein and its cofactor EXTRADENTICLE (EXD) to an
essential and evolutionarily conserved sequence element within the 5'
part of the enhancer (Grieder et al. 1997). Thus, the lab550 enhancer
appears to integrate positional information (via the region-specific expression of the home otic gene lab) and spatiotemporal information (via
DPP signaling); only when these inputs act in concert in an endodermal
cell is the enhancer fully active. These results illustrate how synergistic
effects on an enhancer carrying both DPP- and HOM-responsive sequences can contribute to the generation of a specific cellular response
to DPP; only cells expressing lab can activate this particular DPP-responsive enhancer efficiently.
When these results are interpreted with respect to the possible function of homeotic genes during development, it emerges that one of the
very important roles of homeotic proteins (which are the classic example of proteins conveying positional information to cells in a developing
embryo) is to participate in the interpretation of signaling inputs into
appropriate, position-specific transcriptional responses. Although regulatory cross-talk is a common occurrence in the control of gene transcription, there is little or no precedent for the interaction of homeotic
proteins with those involved in signaling, and I am not aware that such a
direct "signal interpretation" function of the homeotic proteins has been
proposed previously.
Such a proposal is very interesting for discussion in the context of the
developing midgut. As already mentioned, DPP not only induces the
expression of specific genes in the endodermal ceUlayer in the Drosophila embryo, but also in the VM cell layer itself. Genetic studies
provided evidence that the cellular transcriptional response to DPP in
the VM largely depends on the parasegmental provenance of, and thus