wingless
Structure of promoter In Drosophila embryos cubitus interruptus activity is both necessary and sufficient to drive expression of HH-responsive genes, including wingless, gooseberry and patched. To demonstrate that ci is required for transduction of the HH signal, expression of wg was examined in ci null embryos when HH is ubiquitously expressed under control of a heat-shock promoter (Hs-hh). In Hs-hh embryos, wg is expressed ectopically in anteriorly expanded stripes. In ci mutants Hs-hh does not induce ectopic expression of wg. Similar results were obtained for gsb. CI is a sequence-specific DNA binding protein that drives transcription from a wingless promoter in transiently transfected cells. CI binds to the same 9 bp consensus sequence -TGGGTGGTC- as mammalian Gli and Gli3. Alteration of a single nucleotide in the core sequence prevents binding. CI activates transcription from a 5-kb fragment of the wg promoter. CI binding sites in the wg promoter are necessary for this transcriptional activation of. CI element maps to a distal 1-kb region of the 5-kb fragment. The wg promoter sequence has 10 possible Gli consensus binding sites, with three pairs of sites in the distal 1.2 kb. When putatitive CI binding sites are mutagenized, mutant fragments show a greater than 90% reduction in CI-dependent transcriptional activation. Mutagenesis of these sites completely eliminates an electrophoretic mobility shift caused by binding of CI to unmutagenized sites (Von Ohlen, 1997a).
A wingless enhancer region has been described whose Cubitus interruptus (Ci) binding sites mediate Ci-dependent transcriptional activation in transiently transfected cells. Hedgehog (Hh) and Patched (Ptc) act through those Ci binding sites to modulate the level of Ci-dependent transcriptional activation in S2 cells. To test for effects of Ptc and Hh, titrations of Ci cDNA in cultured cells were performed on an expression vector regulated by this enhancer region. The titrations were performed either in the presence of Hh cDNA or in the presence of Ptc cDNA. Reporter activity is reduced 3-fold in the presence of co-transfected Ptc. The addition of Hh results in a 1.5-fold increase in reporter activity over that observed for Ci alone. This same wg enhancer region is Hh responsive in vivo and its Ci binding sites are necessary for its activity. This provides strong evidence that Hh affects wg transcription through post-translational activation of Ci (Von Ohlen, 1997b).
Patterning of the Drosophila embryo depends on the accurate expression of wingless (wg), which encodes a secreted signal required for segmentation and many other processes. Early expression of wg is regulated by the nuclear proteins of the gap and pair-rule gene classes but, after gastrulation, wg transcription is also dependent on cell-cell communication. Signaling to the Wg-producing cells is mediated by the secreted protein, Hedgehog (Hh), and by Cubitus interruptus (Ci), a transcriptional effector of the Hh signal transduction pathway. The transmembrane protein Patched (Ptc) acts as a negative regulator of wg expression; ptc- embryos exhibit ectopic wg expression. According to the current models, Ptc is a receptor for Hh. The default activity of Ptc is to inhibit Ci function; when Ptc binds Hh, this inhibition is released and Ci can control wg transcription. An investigation was carried out of the cis-acting sequences that regulate wg during the time that wg expression depends on Hh signaling. A region consisting of 4.5 kb immediately upstream of the wg transcription unit can direct expression of the reporter gene lacZ in domains similar to the normal wg pattern in the embryonic ectoderm. Expression of this reporter construct expands in ptc mutants and responds to hh activity. Within this 4.5 kb, a 150 bp element, highly conserved between D. melanogaster and Drosophila virilis, is required to spatially restrict wg transcription. Activity of this element depends on ptc, but it contains no consensus Ci-binding sites. The 150 bp G box, 91% identical with its counterart from D. virilis, mediates repression of wg in a ptc-dependent manner. The G box is sufficient for conferring wild-type width to reporter stripes, which in turn expand in a ptc mutant background, thus behaving like wg itself. Deletion of element G result in wide stripes in a wild-type embryo, suggesting that this is a binding site for a transcriptional repressor active in cells anterior to the wild-type wg domain. A repressor that binds element G could possibly act in parallel to ptc and hh; in such a case, the repressor's activity would be overcome by an Hh-regulated activator, i.e. Ci. The simpler explanation is that a repressor functions as another endpoint of Hh signaling. The discovery of an element that is likely to bind a transcriptional repressor was unexpected, since the prevailing model suggests that wg expression is principally controlled by Hh signaling acting through the Ci activator. It is shown that wg regulatory DNA can drive lacZ in a proper wg-like pattern without any conserved Ci-binding sites (Lessing, 1998).
Hox genes encode evolutionarily conserved transcription factors that play fundamental roles in the organization of the animal body plan. Molecular studies emphasize that unidentified genes contribute to the control of Hox activity. This study describes a genetic screen designed to identify functions required for the control of the wingless (wg) and empty spiracles (ems) target genes by the Hox Abdominal-A and Abdominal-B proteins. A collection of chromosomal deficiencies were screened for their ability to modify GFP fluorescence patterns driven by Hox response elements (HREs) from wg and ems. Fifteen deficiencies were found that modify the activity of the ems HRE and 18 that modify the activity of the wg HRE. Many deficiencies cause ectopic activity of the HREs, suggesting that spatial restriction of transcriptional activity is an important level in the control of Hox gene function. Further analysis identified eight loci involved in the homeotic regulation of wg or ems. A majority of these modifier genes correspond to previously characterized genes, although not for their roles in the regulation of Hox targets. Five of them encode products acting in or in connection with signal transduction pathways; this suggests an extensive use of signaling in the control of Hox gene function (Marabet, 2002).
This study surveyed 60% of the genome and 11 genomic regions were found acting as recessive activators of ems HRE; 4 were found acting as recessive repressors of ems HRE, and 18 were found acting as recessive repressors of wg HRE. So far, the only known gene in addition to AbdB required for ems activation is lines. Df(2R)H3E1, which uncovers lines, has been recovered from the screen for AbdB modifiers. A search for discrete mutations that reproduce the deficiency phenotypes allowed identification of four ems HRE modifier genes: dally, ds, scw, and ttk. Although ttk and scw have already been linked to filzkörper development, none of the four genes had previously been involved in the control of ems expression in posterior spiracles. The screen for AbdA modifiers was restricted to genomic regions leading to ectopic activation of the wg HRE; these response elements relate to functions that repress the enhancer. Accordingly, genomic regions or genes already known to play a role in wg activation, such as abdA, exd, hth, or genes coding for components of the Dpp signaling pathway, were not recovered. Five mutations at specific loci reproduce the phenotypes caused by original deficiencies. Four of these mutations identify tsl, ttk, and genes encoding a putative MPK and a putative CBP as candidate modifiers of wg HRE. None of these genes has so far been involved in the regulation of wg in the visceral mesoderm (Marabet, 2002).
Two modifier genes obtained from the wg screen are presumably involved in the signal transduction cascade. The first, tsl, encodes a ligand for the RTK Torso receptor and the second encodes a putative MKP. Signaling by Ras/MAPK could thus be part of the genetic network that controls wg expression in the midgut, which has been confirmed by showing that wg transcription is impaired by a constitutive active form of Ras. Interestingly, the Ras/MAPK pathway has been implicated in regulation of the Ubx and lab enhancer in the central midgut, and the ETS-domain-containing transcription factor Pointed, which acts as a nuclear effector of the Ras/MAPK pathway, is expressed in the third midgut chamber (Marabet, 2002).
Several modifiers of wg and ems HRE activities identified in this study encode molecules acting in signal transduction cascades. This indicates that signaling processes play important roles in the control of Hox gene function and extends previous observations from a screen for modifiers of a dominant Pb phenotype. Understanding how cell signaling and transcriptional control by Hox protein are mechanistically integrated requires further study (Marabet, 2002).
Hox proteins play fundamental roles in generating pattern diversity during development and evolution, acting in broad domains but controlling localized cell diversification and pattern. Much remains to be learned about how Hox selector proteins generate cell-type diversity. In this study, regulatory specificity was investigated by dissecting the genetic and molecular requirements that allow the Hox protein Abdominal A to activate wingless in only a few cells of its broad expression domain in the Drosophila visceral mesoderm. The Dpp/Tgfß signal controls Abdominal A function, and Hox protein and signal-activated regulators converge on a wingless enhancer. The signal, acting through Mad and Creb, provides spatial information that subdivides the domain of Abdominal A function through direct combinatorial action, conferring specificity and diversity upon Abdominal A activity (Grienenberger, 2003).
AbdA is expressed and is active in the third and fourth compartments of the midgut (PS8-PS12), and yet it activates the wg target gene only in PS8. Dpp secreted from PS7 is shown to provide the spatial information required for PS8-localized wg activation and, acting through a newly identified 546 bp enhancer, AbdA and Mad, a transcriptional effector of the Dpp pathway, directly control wg transcription. The convergence of Hox function and Dpp signaling therefore occurs at the levels of DNA and transcription, and endows AbdA with PS8-specific regulatory properties (Grienenberger, 2003).
To identify the enhancer responsible for wg expression in the VM,
subfragments of a 9kb genomic region known to drive wg embryonic
expression were
analyzed in transgenic lines transformed with lacZ reporter
constructs. The
smallest fragment that drives accurate expression in the VM is a 546 bp
XhoI/ClaI (XC) restriction fragment. Its activity is first
detected during germ-band retraction, when wg transcripts are visualized in the VM by in
situ hybridization,
and only in PS8 VM cells. During subsequent development, XC enhancer activity
still mimics wg expression, and is associated with the site of central midgut
constriction formation. Thus, from early on to the end of embryogenesis, the XC
enhancer exclusively and accurately recapitulates wg spatiotemporal
expression in the VM (Grienenberger, 2003).
To address whether AbdA and Dpp signaling could directly regulate wg, the sequence of the XC enhancer was examined for the presence of putative binding sites for AbdA and for Mad/Medea (referred to as DRS, for Dpp response sequence), the canonical transcriptional effectors of the Dpp signaling pathway known to recognize identical target sequences. Since genetic and molecular data led to the proposal that, in Drosophila, the CRE sequences to which Creb proteins bind are required to respond to Dpp in addition to DRSs, potential Creb binding sites were sought. Six TAAT core sequences and four sequences resembling the consensual Hox/Pbx binding sites (TGATNNATG/TG/A) were identified as potentially mediating AbdA function. The Hox/Pbx 3 and 2 sequences strongly match the consensus, with seven or six of the eight consensus nucleotides conserved, respectively. Hox/Pbx sequences 1 and 4 only have five of the eight consensus nucleotides conserved. The XC fragment contains three sequences matching DRSs and two potential CRE sites (Grienenberger, 2003).
To assess the evolutionary conservation of the XC enhancer, an homologous fragment from Drosophila virilis was isolated and analyzed for its in vivo activity by transgenesis in Drosophila melanogaster. The D. virilis fragment drives expression in a pattern very similar to that of the XC enhancer, suggesting that sequences conserved between these two enhancers may be important for wg regulation in the midgut. Sequence comparison, including sequences from D. pseudoobscura, revealed that a majority of the TAAT core motifs, the DRSs and the putative Creb-binding sequences are evolutionarily conserved, whereas sequences that match heterodimeric Hox/Pbx consensus binding sites are not. The existence of two large conserved sequences, Box 1 and 2, is noted. Since Box1 lies in a fragment that does not drive reporter gene expression in transgenic flies, particular attention was paid to Box2 (Grienenberger, 2003).
Hox signaling integration was examined to determine whether signaling pathways contribute towards specifying how AbdA, a widely expressed Hox selector protein, controls the development of distinct pattern elements at different locations. Dpp signal secreted from PS7 provides the positional cue responsible for localized activation of wg by AbdA. Biochemical and reverse genetics experiments have established that AbdA and Mad directly regulate wg transcription through the XC enhancer, which thus serves as an integrator of Hox and Dpp input. AbdA is impotent with respect to this enhancer in the absence of the Dpp signal, though it can function perfectly well on other genes without Dpp. Therefore, functional interactions between selector proteins and signaling pathways confer specificity to signaling pathways, and reciprocally confer functional diversity to selector proteins (Grienenberger, 2003).
This study provides a conceptual framework for understanding the molecular basis of regional Hox protein transcriptional activity. Dpp and Wg signaling subdivide the AbdA Hox domain, allowing activation of pointed (pnt) and opa target genes in the third and fourth midgut chambers, respectively. Based upon the data presented here, it is suspected that the localized activation of pnt and opa by AbdA also relies on direct enhancer integration of Hox and signaling inputs. Accordingly, a Hox/signaling combinatorial code functionally subdivides the domain where a single Hox protein is made, giving rise to discrete patterns of target gene activation. The structures of relevant cis-regulatory regions of AbdA target genes are instrumental for determining which signal is required to allow activation by AbdA. The pnt midgut enhancer would contain AbdA and Wg response elements and would be activated by AbdA specifically in the third midgut chamber through the combinatorial action of AbdA and the Drosophila Tcf/Arm transcriptional effector of Wg signaling. Similarly, the opa midgut enhancer would contain AbdA and Dpp response elements and would be activated only in the fourth gut chamber by AbdA, in this case because of an inhibitory effect of the Dpp-regulated transcription factor on AbdA activity (Grienenberger, 2003).
Further studies are required to understand how Hox selector proteins functionally interact with nuclear effectors of signaling pathways to generate specific transcriptional patterns. In the control of wg by AbdA, several scenarios can be envisioned. In one, the effect of the Dpp transcriptional effector Mad on AbdA activity would be indirect, by antagonizing the function of a repressor that would otherwise act on the XC enhancer to prevent wg expression. The absence of a binding site for this hypothetical repressor in Box2 could explain how Box2 drives AbdA-dependent transcription even without Dpp transcriptional effector binding sites. In a second scenario, Dpp transcriptional effectors would more directly control the activity of AbdA by influencing its DNA binding or transregulatory properties. A direct interaction of HoxC8 and Smad1 has been reported to induce osteoblast differentiation in mammals, suggesting that the coordinate action of AbdA and Dpp signaling might rely on direct AbdA-Mad interaction. In wg regulation, the situation may be different, as additional regulatory inputs are involved. bin and hth are essential, and Wg signaling is required for accurate levels of wg expression. The contribution of Creb might indicate that the Ras/Mapk signaling pathway is involved as well. Ras signaling has been proposed to play a permissive role by acting on CRE sequences of the Ubx and lab enhancers. These observations suggest that AbdA and Hox proteins in general attain specificity and diversity by participating in a variety of protein interactions in enhancer-binding complexes (Grienenberger, 2003).
The precise regulation of wingless (wg) expression in the Drosophila eye disc is key to control the anteroposterior and dorsoventral patterning of this disc. This study identifies an eye disc-specific wg cis-regulatory element that functions as a regulatory rheostat. Pannier (Pnr), a transcription factor previously proposed to act as an upstream activator of wg, is sufficient to activate the eye disc enhancer but required for wg expression only in the peripodial epithelium of the disc. It is proposed that this regulation of wg by Pnr appeared associated to the development of the peripodial epithelium in higher dipterans and was added to an existing mechanism regulating the deployment of wingless in the dorsal region of the eye primordium. In addition, this analysis identifies a separate ventral disc enhancer that lies adjacent to the eye-specific one, and thus altogether, they define a 1-kb genomic region where disc-specific enhancers of the wg gene are located (Pereira, 2006).
During development, a small number of conserved signaling molecules regulate regional specification, in which uniform populations of cells acquire differences and ultimately give rise to distinct organs. In the Drosophila eye imaginal disc, Wingless (Wg) signaling defines the region that gives rise to head tissue. JAK/STAT signaling was thought to regulate growth of the eye disc but not pattern formation. However, this study shows that the JAK/STAT pathway plays an important role in patterning the eye disc: it promotes formation of the eye field through repression of the wg gene. Overexpression of the JAK/STAT activating ligand Unpaired in the eye leads to loss of wg expression and ectopic morphogenetic furrow initiation from the lateral margins. Conversely, tissue lacking stat92E, which cannot transduce JAK/STAT signals, is transformed from retinal tissue into head cuticle, a phenotype that is also observed with ectopic Wg signaling. Consistent with this, cells lacking stat92E exhibit ectopic wg expression. Conversely, wg is autonomously repressed in cells with hyperactivated Stat92E. Furthermore, the JAK/STAT pathway regulates a small enhancer in the wg 3' cis genomic region. Since this enhancer is devoid of Stat92E-binding elements, it is concluded that Stat92E represses wg through another, as yet unidentified factor that is probably a direct target of Stat92E. Taken together, this study is the first to demonstrate a role for the JAK/STAT pathway in regional specification by acting antagonistically to wg (Ekas, 2006).
Although the majority of functions attributable to STATs involve
transcriptional activation, at least one STAT protein, the Dictyostelium Dd-STATa, acts as a
functional repressor. Therefore the ability of Stat92E to directly
repress wg was tested. A reporter called wg2.11Z, in which
ß-galactosidase is driven by a 263 base pair enhancer from the 3'
cis wg genomic region, was sufficient to recapitulate wg
expression in the dorsal margin of the disc proper and in the dorsal
peripodial membrane (Pereira, 2006). This reporter was ectopically expressed in mosaic stat92E clones as well as in stat92E M+ clones in a manner similar to that
observed for wgP. Moreover, wg2.11Z was repressed autonomously in
hop-expressing clones. These data indicate that Stat92E can regulate dorsal
wg expression through the wg2.11Z enhancer. wg2.11Z
does not contain any Stat92E binding sites (TTC(N)3GAA), strongly
suggesting that Stat92E does not repress dorsal wg directly, but
rather regulates another factor which represses wg (Ekas, 2006).
Thus, this paper reports a new role for the Drosophila JAK/STAT
pathway. The study demonstrates that JAK/STAT signaling
promotes formation of the eye field through repression of wg gene
transcription in both the dorsal and ventral halves of the eye disc epithelium. By monitoring Upd
expression and activity, it was shown that the JAK/STAT pathway is normally
activated early in eye development, during first and second instar. Ectopic
activation of this pathway leads to abnormal patterning of the head capsule
and a reduction in the inter-eye distance through an increase in dorsal
ommatidia. By contrast, loss of activity of this pathway, using strong
hypomorphic stat92E mutations, frequently resulted in the development
of a rudimentary head. When the head capsule did form, stat92E
mutants often had small or ablated adult eyes and excessive head cuticle.
wg was ectopically expressed in stat92E clones and
hop mutant eye discs, and was repressed by ectopic activation of the
JAK/STAT pathway. Reduction in the dose of wg partially rescued
stat92E mutants by increasing the rate of eclosion and by mitigating
the phenotypes of stat92E mutant animals. Lastly, it was shown that
wg regulation by the JAK/STAT pathway is independent of the known
wg regulators Eyg, Dac, Hth and Pnr (Ekas, 2006).
These results conflict with those of a previous study, which reported that
JAK/STAT signaling does not repress wg in the eye disc. This
conclusion was reached on the basis of wild-type Wg protein expression in eye
discs that contained ectopic upd-expressing clones (Zeidler, 1999).
However, this study found that in the absence of stat92E, wg was ectopically
expressed in both dorsal and ventral halves of the eye disc. It is likely that
the current examination of the wg gene using the wgP
enhancer trap is a more sensitive measure of wg expression than
monitoring Wg protein. Zeidler also reported that the JAK/STAT
pathway negatively regulates mirr expression. This conclusion was
drawn after finding a preponderance of dorsal, mirr-positive ommatidia in adult eyes containing unmarked upd loss-of-function clones (Zeidler, 1999). However, using marked clones, the current study showed that Mirr is expressed normally in eye tissue that is largely homozygous mutant for stat92E. Moreover, stat92E M+ adult eyes are largely composed of Mirr-negative ommatidia, which indicates their ventral origin. Thus, the current data indicate that mirr is not regulated by JAK/STAT pathway activity (Ekas, 2006).
Previous work has shown that the 3' cis region of the
wg gene regulates its expression in imaginal discs. Several
wg mutations that specifically affect imaginal disc development, as
well as discspecific enhancers, map to this region.
In this study, it was shown that Stat92E negatively regulates dorsal wg
through a small enhancer (wg2.11Z) in the 3' cis
genomic region of the wg gene. This enhancer is ectopically expressed
in stat92E and hop mutants and is autonomously repressed by
ectopic activation of Stat92E. The DNA binding preferences of Stat92E and
other STAT proteins have been well characterized. Because
there are no Stat92E binding sites in the wg2.11Z enhancer,
the interpretation is favoredthat Stat92E does not directly repress dorsal wg
but rather acts through another factor. This repressor may be encoded by a
direct Stat92E target gene, because wg is autonomously repressed by
the JAK/STAT pathway. However, the possibility cannot be ruled out that Stat92E
regulates wg through other transcription factors, such as Dorsal or
vHNF-4, which have putative sites in wg2.11Z
(Pereira, 2006). It is
also possible that there are cryptic Stat92E binding sites in this wg
enhancer, through which Stat92E may directly repress wg. Additional
experiments will be needed to test these possibilities (Ekas, 2006).
This study also demonstrated that Stat92E represses ventral wg in the eye
disc epithelium. This is presumably independent of the wg2.11Z
enhancer, which recapitulates wg expression in the dorsal but not the
ventral eye disc (Pereira, 2006). Moreover, Stat92E negatively regulates
pnr in peripodial cells. In the absence of JAK/STAT signaling,
pnr is dramatically expanded into the posterior peripodial membrane.
However, it is stressed that because pnr is an intracellular protein, the
ectopic pnr in the peripodial membrane cannot account for the ectopic
wg observed in the disc proper of stat92E mutants.
Currently, it is not know whether Stat92E regulates wg in the ventral
eye disc epithelium and the peripodial membrane in the same manner as in the
dorsal eye. All three wg expression domains may be regulated by the
same as yet unidentified factor. Alternatively, Stat92E may regulate
wg expression domains through different mechanisms. For example,
dorsal wg may be regulated indirectly, whereas ventral and peripodial
wg may be regulated directly by Stat92E. The wg gene
3' cis genomic region contains one putative Stat92E binding
site, which resides downstream of the wg2.11Z enhancer. Therefore, it
is possible that Stat92E regulates ventral and peripodial wg through
this site. Future work will be needed to address these issues (Ekas, 2006).
Dependence on signaling from cells of the adjacent anterior compartment Hedgehog is produced by engrailed expressing cells in anterior parasegmental compartments.
Genetic analysis has identified wg transcription in posterior compartments as one of the targets of HH activity. It has been suggested that the spatial control of wg expression depends on the limited range of the HH signal and the differential competence of responding cells. Ubiquitous expression of the hh gene causes the ectopic activation of wg in only a subset of the cells of each parasegment. Competence of cells to express wg is independent of their ability to receive the HH signal (Ingham, 1993).
Localized or ubiquitous expression of the N-terminal domain of HH, a biologically active form of the protein that lacks the normal lipophilic modification, causes an expansion of wingless expression, ventral cuticle defects including a rectangular rather than trapezoidal shape for the denticle belts and loss of denticle diversity, dorsal cutical defects and embryo lethality. This suggests a role for HH autoprocessing (lipid modification) in spatial regulation of hedgehog signaling (Porter, 1996).
Cyclic AMP (cAMP)-dependent Protein kinase A (PKA) is essential during limb development to prevent inappropriate decapentaplegic and wingless expression. A constitutively active form of PKA can prevent inappropriate dpp and wg expression, but does not interfere with their normal induction by hh. It seems that the basal activity of PKA imposes a block on the transcription of dpp and wg and that hh exerts its organizing influence by alleviating this block (Jiang, 1995).
Considered now to be the HH receptor, Patched acts negatively, both in early segment development and in imaginal discs. PTC represses wingless in posterior parasegment domains and acts to repress dpp in the anterior compartment of wing imaginal discs (Schuske, 1994). Unrestricted expression of ptc from a heat-shock promoter has no adverse effect on development of Drosophila embryos. The heat-shock construct can also rescue ptc mutants, restoring wg expression to its normal narrow stripe. This implies that despite its localized requirement, the restricted expression of ptc does not itself allocate positional information (Sampedro, 1991). Thus the role of ptc in positional signaling is permissive rather than instructive, its activity being required to suppress wg transcription in cells predisposed to express wg. According to this view, expression of wg is normally maintained only in those cells receiving an extrinsic signal, encoded by hedgehog, that antagonizes the repressive activity of ptc (Ingham, 1991).
Transient overexpression of ptc in all cells has little or no effect on the segmental pattern. Repeated pulses of ptc production drastically alter the segment pattern to mimic embryos lacking wg. Repeated overexpression results in repression of wg and gooseberry transcription in the germband ectoderm but not in the head. (gooseberry is a wg class segment polarity gene). Expression is unaffected for two other segment polarity genes: engrailed and cubitus interruptus. Thus excess ptc is capable of overcoming the neutralizing signal presumably carried by hedgehog (Schuske, 1994).
Cubitus interruptus is required for wg induction. CI is downstream of ptc and zeste-white 3 which both act negatively on the induction of wg by CI. Fused is required for CI induction of wg (Motzny, 1995).
Misexpression of CI in the Engrailed domain (by placing CI under the control of an en promoter) activates wingless transcription. The expression domains of wingless in such embryos are significantly broader than in wild-type cells. Placing ci under the control of the hairy promoter (hairy is expressed only in alternating parasegments), and testing such a construct in hh mutant embryos, results in a pair-rule phenotype, where every other segment shows naked cuticle. In these embryos, wg expression is present in alternate parasegment. This provides conclusive evidence the CI regulates wingless (Alexandre, 1996).
Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D. The Interactive Fly resides on the
wingless continued: Biological Overview | Evolutionary Homologs |Targets of Activity | Protein Interactions | Developmental Biology | Effects of Mutation | References
Society for Developmental Biology's Web server.