MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
* Author for correspondence (e-mail: mf1{at}mrc-lmb.cam.ac.uk)
Accepted 15 August 2002
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SUMMARY |
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Key words: Drosophila, Wingless, Axin, Eyes absent, Sine oculis, Dachshund, Eye, Transdetermination, Transdifferentiation
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INTRODUCTION |
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The process of compartmentalisation of the eye-antennal imaginal disc
differs significantly from the mechanism used by other imaginal discs. The
eye-antennal discs are primordia of much of the adult head capsule, as well as
of the eyes and antennae. Clonal analysis indicates that AP subdivision only
occurs in the antennal part of the disc
(Morata and Lawrence, 1979).
In the eye anlage, patterning is associated with a wave of neural
differentiation that sweeps across the disc, from posterior to anterior. This
wave of development is preceded by an indentation called the morphogenetic
furrow (Ready et al., 1976
).
In many ways, the furrow represents a dynamic AP border and, like the AP
border of the wing disc, it has long-range patterning abilities
(Baonza and Freeman, 2001
;
Heberlein and Moses, 1995
;
Treisman and Heberlein, 1998
).
Prior to retinal development, which is initiated by the furrow, the
eye-antennal disc is regionally subdivided into head, eye and antennal
domains.
Several genes and signalling pathways are known to contribute to the
subdivision of the eye/antennal disc. The Notch and EGFR pathways are required
for the eye/antennal division (Kumar and
Moses, 2001). The retinal cells are specified during embryonic and
larval stages by the action of the Pax6 transcription factors Eyeless
(Quiring et al., 1994
) and
Twin of eyeless (Czerny et al.,
1999
), in conjunction with the downstream transcription factors
Eyes absent (Bonini et al.,
1993
), Sine oculis (Cheyette
et al., 1994
; Serikaku and
Otousa, 1994
) and Dachshund
(Mardon et al., 1994
). This
hierarchy of transcription factors, which act in a complex series of feedback
loops, comprises a `cassette' of eye specification genes
(Curtiss and Mlodzik, 2000
;
Halder et al., 1998
;
Hazelett et al., 1998
).
Finally, in a role that resembles its function in regional specification in
the wing disc, Wingless participates in distinguishing cells that will form
eye and adjacent head cuticle (Royet and
Finkelstein, 1997
), although the mechanism of this subdivision has
been unclear.
Like several other pathways, Wingless signalling has multiple functions in
eye development. In the third instar disc, Wingless expression is restricted
to the lateral margin, anterior to the progressing furrow, where it prevents
ectopic furrow initiation (Ma and Moses,
1995; Treisman and Rubin,
1995
). Earlier, the localised repression of Wingless by Dpp is
responsible for triggering the initiation of the furrow at the posterior
margin of the disc (Chanut and Heberlein,
1997
; Domínguez and
Hafen, 1997
; Pignoni and
Zipursky, 1997
). In contrast to these processes, little is known
about the function of Wingless in restricting the extent of the eye field
(i.e. defining the border between eye and head cuticle). The observation that
ectopic Wingless signalling prevents eye development
(Lee and Treisman, 2001
;
Royet and Finkelstein, 1997
),
implies that Wingless might regulate the eye specification genes, but current
evidence suggests otherwise: Wingless appears to be genetically downstream of
them (Hazelett et al.,
1998
).
In this work, we have analysed the relationship between the Wingless signalling pathway and the eye specification genes. Our data imply that Wingless signalling initiates the border between eye and head, and thereby controls the specification of the retinal territory, by negatively regulating the expression of eye specification genes. Moreover, we show that Wingless activity can promote developmental plasticity, leading to transdetermination of eye cells.
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MATERIALS AND METHODS |
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Generation of mosaics
Mitotic clones were generated by Flp-mediated mitotic recombination
(Xu and Rubin, 1993).
Recombination was induced different times during the development (60, 84 and
108 hours after egg laying) and by a 1 hour 30 minutes heat shock at 37°C.
Mutant clones in a Minute background for axnh
were marked by the absence of ß-galactosidase staining, using y w
hsp70-flp; FRT82 arm-lacZ M(3)/TM6B stock
(Domínguez et al.,
1998
). These flies were crossed to y w; FRT82
axnh/TM6B. Mutant clones for fz and fz2 were
marked by the absence of GFP crossing males hsp70-flp; tub-GFP
FRT2A by females yw fz fz2 FRT2A/TM6B
Clones of cells expressing GAL4 were induced 24-48 or 48-72 hours after egg laying by 12-15 minute heat shocks at 37°C in flies of the following genotypes:
The flip-out of the <FRT yellow+ FRT> cassette
results in the expression of the transcriptional activator GAL4 gene under the
control of the Act5C promoter
(Ito et al., 1997). Clones
were detected by expression of GFP, and were analysed in third instar
larvae.
axin- clones and axin- clones
expressing UAS-eya1 were generated using the GAL4/GAL80 system
(Lee and Luo, 1999).
UAS-eya FRT82 axnh/TM6B and
FRT82 axnh/TM6B females were crossed to yw
Hs flp tub GAL4 UAS-GFP; tub GAL80 FRT82/+ males.
Scanning electron microscopy
Scanning EM was performed as previously described
(Domínguez et al.,
1998).
Immunohistochemistry
Eye imaginal discs from third instar larvae were stained as described
(Gaul et al., 1992). The
following antibodies were used: rabbit and mouse anti-ß-galactosidase
(Cappel); mouse and rat anti-Elav (used at 1:50 and 1:100, respectively)
(O'Neill et al., 1994
); and
mouse anti-Dll (Díaz-Benjumea and
Cohen, 1995
) and anti-So
(Cheyette et al., 1994
).
Anti-Elav, anti-Eya, anti-Wg and anti-Dac were obtained from the Developmental
Studies Hybridoma Bank at the University of Iowa. Alexa 488- and 594-
(Molecular Probes) and Cy5- (Jackson ImmunoResearch) conjugated secondary
antibodies were used at dilutions of 1:200.
FACS analysis
FACS was performed as described previously
(Neufeld et al., 1998).
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RESULTS |
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Consistent with earlier results in which Wingless signalling was
ectopically activated (Lee and Treisman,
2001; Royet and Finkelstein,
1997
), we find that axin- or
arm* cells show considerable overgrowth and cannot
differentiate as ommatidia. But in contrast to previous reports of ectopic
Wingless signalling early in eye development, we find that the mutant tissue
induces a variety of inappropriate developmental fates
(Fig. 1A-C). Previously, the
mutant tissue has been described as always differentiating as dorsal head
(Royet and Finkelstein, 1997
).
In addition to the frons cuticle with a characteristic ridged appearance that
corresponds to dorsal head, we frequently find other structures including
naked cuticle and tube-like overgrowths with macrochaetae (1C), none of which
correspond to recognisable head structures. Some of the tube-like outgrowths
resemble legs or antennae, although we have not seen specific elements (e.g.
bracts) to confirm this. Therefore, ectopic Wingless signalling can respecify
eye cells to adopt a variety of fates.
|
Given the resemblance of some of the structures caused by ectopic Wingless
signalling to legs and antennae, we have examined whether
axin- or arm* clones express
Distal-less. This gene is required to specify the distal domains of
the leg, antenna and wing discs and is never expressed in the eye disc during
the third larval instar (Kumar and Moses,
2001). Thus, its ectopic expression would indicate a change of
fate from eye to leg, antenna or wing. Approximately 5% of clones
(n>100) did indeed express Distal-less
(Fig. 1D); notably, the ectopic
expression of Distal-less was always associated with tube-like
overgrowth in the disc (Fig.
1E-G). This result confirms our conclusion that eye cells
receiving ectopic Wingless signal are not only transformed to dorsal head
structures. Instead, Wingless signalling respecifies eye cells into a variety
of fates, which include head cuticle, but also include more dramatic
transformations to cells with properties of legs and/or antennae. This
phenomenon resembles transdetermination, which has been shown to be promoted
by Wingless in other Drosophila tissues
(Johnston and Schubiger, 1996
;
Maves and Schubiger,
1998
).
Ectopic Wingless signalling disrupts proliferation in the eye
disc
One of the phenotypes caused by the ectopic activation of Wingless in the
eye discs is tissue overgrowth. In the eye discs, as in other tissues,
differentiation is accompanied by the cessation of cell proliferation; all the
cells are arrested in G1 in the morphogenetic furrow. After the furrow, those
cells not incorporated into the precluster undergo one more division, known as
the second mitotic wave (Ready et al.,
1976). We compared the cell cycle state of wild-type and
axin- cells from eye/antennal discs containing large
numbers of clones with ectopic Wingless activation; in these discs, the mutant
cells expressed GFP [using the Gal4/Gal80 system
(Lee and Luo, 1999
)] so could
be separated from wild-type cells by FACS sorting. Forty-two percent of
wild-type cells were in G1, whereas 24% and 34% were in S and G2, respectively
(Fig. 2A, black trace). Note
that most of the wild-type cells in S or G2 are actually in the antennal
region of the disc or anterior to the morphogenetic furrow: immunostaining
shows few in the posterior eye region, these being limited to the second
mitotic wave (Baker and Yu,
2001
). In the same eye/antennal discs, axin-
cells (Fig. 2A, red trace)
showed a significant increase in the proportion of cells in S and G2 (30% and
38%, respectively), at the expense of cells in G1 (32%). In conjunction with
the observation that overgrowth is seen in axin- and
arm* clones anterior to the furrow, but is much greater on
average in clones posterior to the furrow, this indicates that cells receiving
excess Wingless signalling overproliferate and are not arrested by the passage
of the furrow. Consistent with this conclusion, we observe substantial excess
BrdU incorporation posterior to the furrow in axin- clones
(Fig. 2B).
|
Ectopic Wingless signalling represses eye selector genes
The loss of eye identity caused by the ectopic activation of Wingless,
suggests a possible function for Wingless in the regulation of the eye
selector genes. The top of the genetic hierarchy involved in eye specification
appears to be the Pax6 homologue, Eyeless
(Halder et al., 1995;
Quiring et al., 1994
). In the
third instar eye disc the expression of Eyeless is restricted to the region
anterior to the furrow and, despite the Wingless-induced inhibition of eye
development, the expression of Eyeless in this region is not affected by
axin- clones (Lee and
Treisman, 2001
). This lack of an effect anterior to the furrow,
despite the overgrowth and abnormal Distal-less expression in the same region,
implies that misregulation of Eyeless is not the primary cause of the
transformations caused by ectopic Wingless activity.
Downstream of Eyeless (although feedback relationships makes the epistatic
relationship complex) are other transcription factors required for eye
specification, including Eyes absent, Sine oculis and Dachshund
(Bonini et al., 1993;
Cheyette et al., 1994
;
Mardon et al., 1994
;
Serikaku and Otousa, 1994
). A
phenotype similar to axin- clones of excess proliferation
and consequent overgrowth is caused by loss of Eyes absent and Sine oculis
(Pignoni et al., 1997
).
Moreover, as in axin- clones
(Lee and Treisman, 2001
),
clones mutant for sine oculis ectopically express Eyeless in the
region posterior to the furrow [see fig.
3G by Pignoni et al. (Pignoni
et al., 1997
)]. The similar mutant phenotypes shown by the loss of
function of these genes and the ectopic activation of Wingless signalling make
them good candidates to be regulated by the Wingless pathway.
|
We therefore analysed the expression pattern in third instar eye discs of
Eyes absent, Sine oculis and Dachshund in axin- and/or
arm* mutant clones. At this stage, Dachshund is expressed
at high levels on either side of the morphogenetic furrow, whereas Eyes absent
and Sine oculis are expressed in all the cells of the eye primordium (see Figs
5,
6)
(Bonini et al., 1993;
Cheyette et al., 1994
;
Curtiss and Mlodzik, 2000
;
Mardon et al., 1994
). In order
to produce large patches of mutant tissue, we have used the Minute
technique (Morata and Ripoll,
1975
). We find that in axin-
M+ clones the expression of Eyes absent in front of the
furrow is always autonomously eliminated
(Fig. 3). This effect is not
only seen in large clones that touch the eye margin but also in small internal
clones (Fig. 3A,I-K). Identical
results were obtained with Sine oculis and Dachshund: their expression was
autonomously lost from anterior axin-
M+ clones (not shown). Consistent with these results, in
arm*-expressing clones Eyes absent, Dachshund and sine
oculis (detected with a lacZ reporter construct) were similarly
autonomously eliminated (Fig.
4A-C). We therefore conclude that Wingless signalling represses
the expression of the eye selector genes eyes absent, dachshund and
sine oculis anterior to the morphogenetic furrow. Posterior to the
furrow, however, some clones express high levels of Eyes absent (e.g.
Fig. 3A,B,F-H;
Fig. 4C), and Dachshund (e.g.
Fig. 4B). This effect is always
associated with overgrowth, and this expression is restricted to only some
cells in these clones.
|
|
|
In order to analyse the temporal requirement of the Wingless pathway in the regulation of Eyes absent, we have induced axin- M+ clones at different stages of eye development. We find that ectopic expression of Wingless is sufficient to repress Eyes absent throughout the whole of eye disc development. However, in some clones anterior to the furrow that were induced very late [from mid-third instar onwards (108 hours AEL); Fig. 3I-K], we saw a small number of cells expressing low levels of Eyes absent (Fig. 3J, arrow). We do not understand the basis of this expression in all other contexts the loss of Eyes absent was complete but the effect was weak and the number of cells small. The fact that it is only seen in the latest induced clones suggests that it may represent slight perdurance of Axin within some cells in the clone.
We also examined axin- clones in a non-Minute
background, using the Gal4/Gal80 expression system
(Lee and Luo, 1999) to mark
the mutant clones positively (red in Fig.
5). This approach complemented the above analysis in three ways.
First, it allowed us to confirm that the excess growth in
axin- clones was independent of the Minute
background (Fig. 5A, blue
section). Second, it allowed us to see the mutant cells more clearly as they
were marked in red (Fig.
5A,B,D); this allowed a clearer visualisation of the overgrowth,
especially when it was outside the plane of the normal disc epithelium (e.g.
arrow in blue, transverse section of Fig.
5A). Third, it confirmed the autonomous loss of Eyes absent
(Fig. 5A, red transverse
section), Dachshund (Fig. 5C,
arrowhead) and Sine oculis (Fig. 5D and
inset in E) in even small clones anterior to the morphogenetic
furrow.
Eyes absent and Sine oculis have complementary expression patterns to
Wingless in the eye disc
The conclusion that Wingless signalling negatively regulates the expression
of Eyes absent, Dachshund and Sine oculis anterior to the furrow leads to the
prediction that in normal development, domains of high Wingless activity in
the anterior region of the eye disc will be associated with low expression of
these genes. Previous work indicates that their expression is broadly
non-overlapping, but to analyse this precisely we have double-labelled discs
to detect the expression of Wingless and Eyes absent of Sine oculis throughout
the third instar larval stage. The expression of these eye specification genes
is precisely complementary to that of Wingless in the anterior lateral margins
of the eye throughout the third instar
(Fig. 6). This is consistent
with a role for Wingless signalling in initiating the borders between eye and
other head structures. Note that in posterior lateral regions we observe
slight overlap between the expression of Wingless and these genes; this is
presumably analagous to the expression of eye specification genes we see in
some posterior axin- clones, and confirms that in
posterior regions of the eye disc, Wingless signalling is not incompatible
with the expression of these genes.
In the most anterior region of the eye portion of the disc, there is a domain in which Eyes absent, Sine oculis and WglacZ are expressed (e.g. Fig. 6B). Although this could imply other factors being necessary for the repression of Eyes absent and Sine oculis in this region, we favour the idea that Wingless protein reaches these cells from the adjacent lateral expression domains. This is supported by our observation that loss of Wingless signalling in this domain (in fz-, fz2- clones) leads to the ectopic expression of eye specification genes (see below).
Loss of Wingless signalling causes the ectopic expression of Eyes
absent and Dachshund
The data presented above analyse the effects of ectopic activation of
Wingless signalling. The results suggest that in normal development Wingless
signalling is responsible for blocking the expression of eye selector genes
like Eyes absent and Dachshund, thereby regulating the extent of the eye
field. However, drawing firm conclusions from the consequences of ectopic
signalling is unreliable, so we examined the consequences of loss of Wingless
signalling, which would be predicted to cause the ectopic expression of the
Wingless-repressed eye specification genes. In order to generate a complete
loss of Wingless reception, we made clones lacking both Wingless receptors:
Frizzled and Frizzled 2 (Bhanot et al.,
1999; Chen and Struhl,
1999
). We find that in these double mutant clones, Eyes absent and
Dachshund are ectopically expressed in the lateral margin anterior to the
furrow and the most anterior region of the eye primordium (vertex primordium)
(Fig. 7A-C). With low frequency
these clones also cause the differentiation of ectopic ommatidia on the dorsal
adult head (not shown). This is consistent with a previous observation that
loss of dishevelled (Heslip et
al., 1997
), which encodes a component of the Wingless signal
transduction pathway (Klingensmith et al.,
1994
; Theisen et al.,
1994
), also leads to the formation of ectopic ommatidia. These
double mutant clones also show slight overgrowth. These results confirm the
conclusions of the ectopic expression experiments and demonstrate that
Wingless signalling inhibits the inappropriate expression of eye specification
genes in normal eye development.
|
The phenotype of ectopic Wingless activation is not rescued by the
expression of Eyes absent
The hierarchy of genes required for the eye specification is complex but
there is strong evidence to place Eyeless at the top of the cascade. Eyeless
activates the expression of eyes absent and sine oculis,
which in turn trigger the initiation of dachshund expression;
positive feedback between these genes stabilises and maintains their
expression (Bonini and Choi,
1995; Chen et al.,
1997
; Curtiss and Mlodzik,
2000
; Halder et al.,
1998
; Niimi et al.,
1999
; Pignoni et al.,
1997
; Zimmerman et al.,
2000
). We have shown that Wingless activity represses the
expression of eyes absent, sine oculis and dachshund (Figs
3,
4,
5). The repression of
dachshund is presumably a consequence of the loss of Sine oculis and
Eyes absent, but the epistatic relationship between sine oculis and
eyes absent is complicated and it has not been determined whether
they act in parallel downstream of eyeless, or if sine
oculis is downstream of eyes absent
(Curtiss and Mlodzik, 2000
;
Desplan, 1997
;
Halder et al., 1998
;
Pignoni et al., 1997
). To
address the issue of where Wingless acts in this network, we tested whether
the expression of Eyes absent in axin- clones [using the
Gal4/Gal80 system (Lee and Treisman,
2001
; Lee and Luo,
1999
)] was sufficient to rescue their phenotype. The phenotype of
these clones is very similar to the axin- control clones
(compare Fig. 8 with
Fig. 5): neural differentiation
is abolished (not shown) and large tube-like overgrowths are observed. However
the expression of Dachshund (Fig.
8A) and Sine oculis (Fig.
8B) is partially rescued in at least some clones anterior to the
furrow, implying that Eyes absent can be sufficient to trigger their
expression, even when Wingless signalling is high. This is confirmed by the
fact that Sine oculis is often ectopically expressed in these clones in the
antennal region of the disc (Fig.
8B, inset). We conclude that the expression of Eyes absent is not
sufficient to rescue the whole phenotype caused by ectopic Wingless activity
in the eye but can activate the expression of Sine oculis and Dachshund at
least to low levels.
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DISCUSSION |
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Further support for our model is derived from previous analysis of eye
specification genes. For example, ubiquitous expression of Eyeless in the wing
imaginal disc causes activation of Eyes absent and Sine oculis, but only in
cells close to the AP border that do not express Wingless
(Halder et al., 1998).
Furthermore, loss of Eyes absent and Sine oculis cause very similar
overgrowths to those we have observed in axin- or
arm* clones. This overgrowth presumably represents a
combination of hyper-proliferation in the anterior regions, and the loss of
eye identity in mutant cells so that they no longer respond to the passage of
the morphogenetic furrow by arresting in G1; instead they continue to
proliferate, as evidenced by the increase of cells we observe in G2.
We therefore propose that the initial expression of Eyes absent, Sine
oculis and Dachshund is negatively regulated by Wingless signalling in the eye
disc, and that this regulation initiates the border between the eye field and
adjacent head cuticle. We have attempted to define whether Wingless represses
the eye specification genes independently or whether eyes absent is
the primary target but our data confirms earlier reports of the complexity of
the regulatory relationships between eyes absent, sine oculis and
dachshund. Our observation that Eyes absent is able partially to
restore the expression of the other two genes but cannot rescue the overgrowth
and differentiation phenotype of axin- clones has two
possible explanations. Either Wingless represses eye development through at
least one additional gene, or high level Wingless signalling blocks eye
development later in the developmental program [e.g. it is known to inhibit
morphogenetic furrow initiation (Ma and
Moses, 1995; Treisman and
Rubin, 1995
)], even after its earlier effects are rescued by
eyes absent expression.
Despite the clear evidence for Wingless repressing the eye specification
genes anterior to the morphogenetic furrow, we find some mutant cells that
express Eyes absent, Sine oculis and Dachshund posterior to the furrow. The
fact that these mutant cells do not differentiate as eye indicates that this
late expression is not enough to induce eye differentiation. We do not fully
understand this phenomenon, but we speculate that eye specification requires
these genes to be expressed only in front of the furrow, whereas behind the
furrow they may have a separate function in differentiation and be regulated
differently. Consistent with this hypothesis, the late expression of Eyes
absent behind the furrow is required for differentiation of the photoreceptors
(Pignoni et al., 1997), and
the paramount eye selector gene Eyeless is expressed only anterior to the
furrow at this stage (Quiring et al.,
1994
). Furthermore, this interpretation is consistent with our
observation that in posterior regions of the eye disc, there is a slight
overlap between the expression of Wingless and the eye specification
genes.
During eye disc development, Wingless signalling represses Dpp activity and
vice versa (Domínguez and Hafen,
1997; Hazelett et al.,
1998
; Ma and Moses,
1995
; Treisman and Rubin,
1995
; Wiersdorff et al.,
1996
). In addition to the mutual repression of these two pathways
during morphogenetic furrow initiation, it has been proposed that in the early
eye disc, Dpp prevents head fate by repressing Wingless
(Royet and Finkelstein, 1997
).
Can the data we present here be explained by this mutually repressive
relationship between Wingless and Dpp? Although the loss of Dpp during the
early stages of eye disc development resembles the activation of Wingless
signalling in some regards, the axin- and
arm* clones have other phenotypes that do not correspond
to loss of Dpp signalling. Thus, after the furrow is already initiated, Mad
clones downregulate Eyes absent and Dachshund only when they are at the margin
of the disc (Curtiss and Mlodzik,
2000
). This contrasts with our observation that Wingless represses
the expression of eyes absent, sine oculis and dachshund in
all anterior cells throughout eye disc development, regardless of whether they
are marginal or interior. Furthermore, the overgrowth phenotypes caused by the
ectopic activation of Wingless signalling are not found in
mad- clones (Curtiss
and Mlodzik, 2000
; Hazelett et
al., 1998
). Therefore, although some of the effects of ectopic
Wingless activity may be a consequence of the downregulation of Dpp
signalling, others must be caused by Dpp-independent mechanisms.
Note that, while highlighting the role of Wingless signalling as an important physiological regulator of the size of the eye, our data do not address how direct the effect of Wingless is on the expression on eyes absent, sine oculis and dachshund. It is possible that this represents a direct transcriptional repressor function for Wingless signalling, but it is equally possible that Wingless induces the expression of a repressor of these eye specification genes.
Very recently, Lee and Treisman reported the phenotype of
axin- clones in the eye imaginal disc. They too reported
the overgrowth phenotype that we have described, but otherwise they examined
different aspects of the phenotypes of these clones. Based on that analysis
they proposed a different model: that Wingless signalling normally promotes
the proliferation of cells anterior to the morphogenetic furrow, and that the
ectopic activation of this pathway behind the furrow is sufficient to maintain
cells in an anterior state in which they proliferate, fail to differentiate
and continue to express anterior markers
(Lee and Treisman, 2001). Some
of our results, such as the high levels of Eyes absent and Dachshund found in
posterior axin- clones, are consistent with this model but
several others are not. Thus, the loss of eye identity in
axin- clones is not consistent with those cells being held
in an anterior eye state; nor is the loss of expression of eye specification
genes that are normally expressed in the anterior of the eye field; nor,
finally, is the ectopic expression of Eyes absent caused by loss of Wingless
signalling. For these reasons, we believe that our interpretation of Wingless
activity being a regulator of the eye specification genes more completely fits
the existing experimental evidence.
Wingless and transdetermination
Wingless signalling is required to distinguish wing pouch cells from notum
cells (Ng et al., 1996). We
and others (Heslip et al.,
1997
; Royet and Finkelstein,
1997
) have described a similar function of Wingless during eye
disc development in defining the border between retina and adjacent head.
However, we have found that in addition to dorsal head cuticle, the
axin mutant cells can transform the eye cells into other tissues. For
example, we have shown that the axin- clones sometimes
express Distal-less, a gene not expressed in the third instar eye but
specific to the leg, wing and antennal discs. This fits with previous reports
that ectopic expression of Wingless during the development of other imaginal
discs can induce transdetermination the change of cell identity from
one fate to another (Johnston and
Schubiger, 1996
; Maves and
Schubiger, 1998
). The plasticity of mammalian cells during
development is a hotly debated issue that has important implications for the
potential utility of stem cells. It may be that, as in other fields,
Drosophila genetics can shed some light on the mechanisms of
developmental plasticity and how they are regulated.
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ACKNOWLEDGMENTS |
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