1 Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch,
Robert-Rössle Strasse 10, D-13125 Berlin-Buch, Germany
2 Howard Hughes Medical Institute, Departments of Physiology and Biochemistry,
University of California, 533 Parnassus Avenue, San Francisco, CA 94143-0725,
USA
* Author for correspondence (e-mail: salim{at}mdc-berlin.de)
Accepted 6 January 2003
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SUMMARY |
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Key words: Bazooka, Cell invasion, Border cell migration, Cell polarity, Discs large, Drosophila melanogaster, Follicle cell, Cell adhesion
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INTRODUCTION |
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Border cell migration during Drosophila oogenesis is one
well-studied example of invasive and directed migration
(Spradling, 1993;
Montell, 2001
;
Rørth, 2002
). Border
cells are specified within the anterior follicular epithelium that surrounds
the germ cells in each egg chamber (Fig.
1). At late egg chamber stage 8, approximately eight border cells
delaminate from the monolayer epithelium and, in a highly stereotyped fashion,
invade the germ cell cluster within the developing egg chamber
(Montell et al., 1992
;
Niewiadomska et al., 1999
).
First, they undergo directed cell migration between nurse cells towards the
anterior margin of the oocyte and then turn dorsally, coming to rest at the
dorsal anterior corner of the egg chamber next to the underlying oocyte
nucleus.
|
The Drosophila tumor suppressor genes discs large (dlg 1
FlyBase) and lethal (2) giant larvae (lgl; l(2)gl FlyBase)
play essential roles in epithelial cell polarity, adhesion and proliferation
(Mechler et al., 1985;
Jacob et al., 1987
;
Woods and Bryant, 1989
;
Woods and Bryant, 1991
;
Woods et al., 1996
;
Woods et al., 1997
;
De Lorenzo et al., 1999
;
Bilder et al., 2000
). Follicle
cell epithelia mutant for dlg undergo an epithelial-to-mesenchymal
transition driving their invasion between germ cells, in a pattern similar to
that observed in migrating border cell clusters
(Goode and Perrimon, 1997
).
Within follicle cells, Dlg localizes to the basolateral membrane and, in germ
cells, the protein is present at sites of contact between germ cells. However,
the protein is conspicuously absent from sites of contact between follicle and
germ cells raising the question as to whether dlg affects the
follicle and germ cell interactions indirectly via another protein
complex.
The apical Drosophila Bazooka (Baz), Par-6 (DmPar-6), and atypical
protein kinase C (DaPKC/aPKC) protein complex (in this text referred to
collectively as the PAR complex) regulates apical-basal polarity in a variety
of epithelial and nonepithelial cell types and is functionally conserved among
different organisms (Jan and Jan,
1999; Doe, 2001
;
Knoblich, 2001
). Central to
the assembly of this complex are the PDZ domain scaffolding proteins Baz and
DmPar-6 (Kuchinke et al.,
1998
; Petronczki and Knoblich,
2001
) which together with DaPKC form a subapical membrane protein
complex in polarized epithelial cells, where they function to stabilize
adhesion complexes at the apical adherens junctions
(Wodarz et al., 2000
).
In zebrafish, loss of atypical protein kinase C (aPKC
)
causes severe epithelial defects and loss of cell polarity
(Horne-Badovinac et al., 2001
;
Peterson et al., 2001
).
Furthermore, within the context of an in vitro wound assay, using primary
migratory rat astrocytes, and upon integrin-mediated activation of Cdc42, an
mPar6/aPKC
complex is recruited to the wound leading edge where it
initiates the establishment of cell polarity
(Etienne-Manneville and Hall,
2001
).
In this study, we compared the function of baz in two distinct types of follicle cell invasion: border cell migration and dlg tumor cell invasion. We demonstrate that the tumor suppressor genes dlg and lgl function cell-autonomously within follicle cells to prevent invasion and that baz acts downstream of dlg in mediating follicle cell invasion, revealing that wild-type baz activity is required for dlg mutant follicle cell invasion. Clonal analysis of dlg baz double mutant follicle and germ cell clones suggests that baz regulates adhesion among migrating follicle cells, as well as between these cells and their substratum. In contrast, neither baz nor DaPKC appears to be required for border cell invasion and migration per se, since mutant border cells appropriately migrate, reaching the anterior margin of the oocyte at the expected stage. However, border cells mutant for baz appear to be deficient in their adhesion to each other and frequently display an altered arrangement of the border cell cluster.
Collectively, these results provide evidence for interactions between components of the basolateral and apical cell-cell junctions in the context of tumorous follicle cell invasion in the ovary, mediated by Dlg and Baz, respectively. Furthermore, our data suggest a role of baz in differentially regulating adhesion among distinct types of invasive follicle cells and show that border cell and dlg tumor cell invasion can mechanistically be differentiated via the function of baz.
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MATERIALS AND METHODS |
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The following strains were used to generate germline clones by the FLP/FRT
technique (Xu and Rubin,
1993): yw bazEH171
P[mini-w+, FRT]9-2/FM6, yw B; pr pwn
P[ry+; hsFLP]38/CyO, y
dlgm52 P[mini-w+, FRT]101
/FM6, yw B; pr pwn P[ry+;
hsFLP]38/CyO, yw P[w+; ubi-nls-GFP]
P[mini-w+, FRT]9-2, yw
P[w+; ubi-nls-GFP] P[mini-w+,
FRT]101, yw; P[ry+, FRT]42D
DaPKCk06403/CyO, yw P[mini-w+,
hs-FLP]1; P[ry+, FRT]42D
P[mini-w+; ubi-nls-GFP]2R/CyO, yw
P[mini-w+, hs-FLP]1;
l(2)gl4 P[en.lacZ]2L P[ry+,
FRT]40A/CyO, yw P[mini-w+,
hs-FLP]1; P[mini-w+; ubi-nls-GFP]2L
P[ry+, FRT]40A/CyO, yw dlgm52
bazEH171 P[mini-w+,
FRT]9-2/FM6, yw B, yw P[w+;
ubi-nls-GFP] P[mini-w+, FRT]9-2, pr
pwn P[ry+; hsFLP]38/CyO, yw B, pr
pwn P[ry+; hsFLP]38/CyO. The
P[w+; ubi-nls-GFP] P[mini-w+, FRT]
chromosomes bear a polyubiquitin promoter that drives ubiquitous nuclear GFP
expression. Administering a 1-hour heat shock at 37°C on several
consecutive days during late larval and pupal stages induced germline clones.
Following immunohistochemistry, germline clones were identified by the absence
of nuclear GFP expression.
Immunohistochemistry and imaging
Wild-type and mosaic ovaries were dissected, fixed and stained as described
previously (Cox et al., 2001a).
The following antisera were used: rabbit anti-Baz (1:1,500; a gift from A.
Wodarz, Düsseldorf); rabbit anti-PKC
C20 (1:1000; Santa Cruz
Biotechnology); guineapig anti-Dlg (1:1000; a gift from P. Bryant); rabbit
anti-Slbo (1:100; a gift from P. Rørth, EMBL Heidelberg); mouse
anti-FasIII 7G3 (1:25; Developmental Studies Hybridoma Bank, University of
Iowa); rat anti-Dcad2 (1:50; a gift from T. Uemura); mouse anti-Arm (1:100,
N2-7A1 Developmental Studies Hybridoma Bank, University of Iowa); rabbit
anti-ßH-spectrin [1:25
(Thomas and Kiehart, 1994
)].
Cy2-, rhodamine red X- and Cy5-conjugated secondary antibodies (Jackson
ImmunoResearch; Molecular Probes) were used at 1:200 to 1:500. Fluorescently
labeled samples were counterstained with propidium iodide to visualize DNA.
Micrograph images were taken with either BioRad MRC 1024ES confocal laser
mounted on a Nikon Eclipse TE300 microscope or a Leica TCS SP2 laser scanning
spectral confocal microscope. Images were processed with Adobe Photoshop
(Adobe Systems).
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RESULTS |
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|
|
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Baz and DaPKC protein localization within the border cell
cluster
To further investigate the roles of baz and DaPKC during
invasive cell migration, we characterized their function during border cell
migration, a process that bears many similarities to tumor cell invasion
(Montell, 2001). The border
cell cluster comprises the two polar or central cells in the anterior
follicular epithelium and several surrounding rosette cells that carry the
central polar cells along as they migrate
(Niewiadomska et al., 1999
).
The two central polar cells can specifically be labeled with anti-Fasciclin
III antibodies (Brower et al.,
1980
; Patel et al.,
1987
) and the whole cluster of migrating cells can be marked with
anti-Slow border cells (Slbo), the Drosophila homolog of C/EBP, a
transcriptional activator that is essential for border cell migration
(Montell et al., 1992
). We
first analyzed the distribution of Baz and DaPKC proteins within the border
cell cluster. At late stage 8, when border cells segregate from the follicular
epithelium, both Baz and DaPKC proteins display a tight apical localization to
the junctional zone and reduced uniform levels of expression along all surface
membranes (Fig. 5A).
|
baz affects adherence within the border cell cluster
We next tested whether baz and DaPKC function during
border cell migration. In bazEH171 and
DaPKCk06403 mutant follicle cell epithelia, specification
of central polar border cells was mostly normal as indicated by the presence
of FasIII positive cells (Fig.
6A,B; and not shown). In addition, bazEH171 or
DaPKCk06403 mutant rosette cells (S1bo-positive) were
present (Fig. 6D-H,J).
Therefore, neither baz nor DaPKC is required for border cell
specification.
|
In the case of DaPKC, no defects in border cell migration were observed. Border cell mosaic clones in which all rosette cells were mutant for DaPKCk06403, migrated properly to the anterior margin of the oocyte. Moreover, adherence of mutant cells within the border cell clusters was unaffected (Fig. 6J). Based on these results, we conclude that baz is dispensable for both border cell invasion and motility, but appears to play a role in the adherence among border cells within the cluster, however, a similar requirement for DaPKC was not detected in this process.
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DISCUSSION |
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baz differentiates tumor cell from border cell invasion
Two lines of evidence suggest mechanistic differences between tumor cell
and border cell invasion. First, while both dlg tumor cell and border
cell invasion undergo a series of similar morphogenetic behaviors, the
molecular mechanisms regulating each cellular repertoire appear, at least in
part, to be distinct. Whereas tumor cell invasion is dependent on
baz, border cell invasion and motility are not. Therefore,
baz genetically discriminates between these processes. Conversely,
border cell migration requires slbo function, whereas dlg
mutant follicle cell invasion can occur with much lower levels of Slbo and
FasIII proteins and therefore dlg mutant cells appear not to adopt a
border cell fate (Goode and Perrimon,
1997). A second line of evidence for mechanistic differences is
that the patterns of cell invasion are distinct. The timing, direction and
cohesion of border cells during their migration is highly stereotyped. In
contrast, dlg tumor cells can invade at any stage in egg chamber
development and in any orientation relative to the oocyte, possibly due to the
position where follicle cell over-accumulation and multi-layering occur.
Moreover, invasion also occurs in the absence of an oocyte, for example when
the germline is dlgm52 bazEH171 double
mutant.
Our data suggest that wild-type Baz is a permissive factor required for follicle cell invasion but that baz gene function is dispensable for border cell specification and invasion. Therefore, in the absence of baz, the specification of Slbo-positive cells and activation of the appropriate downstream targets that are required for the orchestration of border cell migration is normal. The activation of slbo and its target genes may largely mask the permissive role of baz in follicle cell migration, a requirement that is uncovered in the context of the slbo-independent type of follicle cell invasion caused by the loss of dlg. Moreover, in contrast to DE-cadherin, another gene with an essential function during border cell migration, Baz and DaPKC levels are not increased in border cells prior to and during border cell migration. The defects observed in baz mutant border cell migration are best explained by the lack of adhesion within the border cell cluster rather than by migratory defects.
This interpretation is consistent with the observation that, during border
cell migration, baz function is clearly distinct from that of
DE-cadherin, which, though essential for cell motility, does not
affect border cell adhesion. The requirement of DE-cadherin for border cell
motility appears to be independent of its role as a structural component of
the ZA since another essential ZA component, the cytoskeletal linker protein
Armadillo, is not required for border cell migration
(Peifer et al., 1993). In
mosaic border cell clones with DE-cadherin mutant cells, the mutant
cells consistently lag behind wild-type cells, indicating that the mutant
cells have a compromised migratory ability and that they are being dragged
along by their wild-type neighbor cells
(Niewiadomska et al., 1999
).
Conversely, in mosaic border cell clones, bazEH171 mutant
cells were found in every position within the migrating border cell clusters,
including the leading position, indicating normal motility. Indeed, cohesion
between the migrating cells appears to be defective as mosaic cell clones were
frequently dispersed and misarranged. Therefore, baz and
DE-cadherin appear to have different functions during border cell
migration.
A model for baz function during tumor cell invasion in the
Drosophila ovary
This study provides an example of a genetic interaction between the apical
PAR complex and basolateral tumor suppressor genes. This interaction was
assessed based on tumor cell invasion. We have demonstrated that baz
is epistatic over dlg in regulating this process. One possible
explanation for the mechanism by which Dlg, a basolateral protein absent from
the sites of contact between follicle and germ cells, regulates motility is
that it acts via another protein complex. In this study, we have presented
evidence that the apical PAR complex may serve such a function. We suggest a
model in which follicle cell invasion is a two-step process: first, the loss
of dlg releases a repression of motility and, second, the apical PAR
complex protein Baz serves as a permissive factor for invasion (see model,
Fig. 7). Based on our mosaic
analysis, we propose a model in which invasion might be mediated by two
separate baz-dependent interactions between follicle and germline
cells. During invasion of dlg mutant follicle cells, Baz functions as
a permissive factor to promote follicle cell invasive behavior
(Fig. 7B). This invasive
behavior is blocked in the absence of follicle cell Baz
(Fig. 7C), as
dlgm52 bazEH171 or bazEH171
mutant follicle cells lack invasive properties. Within the germline, Baz
functions as both a permissive factor during invasion of
dlgm52 mutant follicle cells that express Baz, possibly by
stabilizing adhesion between the invading somatic cells and the germline cells
(Fig. 7B) and, in the absence
of follicle cell Baz, as a repressor of follicle cell invasion, possibly by
regulating germ cell adhesion and preventing invasion of Baz-deficient
follicle cells (Fig. 7C). The
repression of Baz-deficient follicle cell invasion is neutralized in
dlgm52 bazEH171 mutant germ cell clones
possibly by a reduction of germ cell adhesion that may increase the ease with
which dlgm52 bazEH171 mutant follicle cells can
invade (Fig. 7D). These
observations raise the question as to the molecular machinery and the adhesion
molecules that mediate baz-dependent invasion and to the mechanisms
that are in place in dlgm52 bazEH171 mutant
follicle and germ cells in which invasion occurs. An alternative explanation
to the loss of motility is that the removal of a second cell polarity system
from follicle cells may cause such severe disturbances as to prevent cell
invasion. However, dlgm52 bazEH171 double
mutant follicle cells retain their capability to invade into
dlgm52 bazEH171 double mutant germline proper,
contradicting this explanation.
|
In contrast to previous findings reported by Goode and Perrimon
(Goode and Perrimon, 1997),
our results indicate dlg predominantly functions cell-autonomously to
prevent invasion of follicle cells. This finding is consistent with our data
on lgl, which also functions cell-autonomously within the follicle
cell layer to prevent heterogeneous cell mixing and invasion. Indeed, Goode
and Perrimon documented cases of cell-autonomous invasions of follicle cells
into the germline, which support the notion that, despite quantitative
differences between the studies, dlg functions cell-autonomously
within the follicle cell layer. The FLP/FRT technique combined with GFP
imaging used in our study allows for the unambiguous identification of mosaic
tissues, clarifying issues of cell-autonomous gene function.
The multiple PDZ domain protein Baz and its vertebrate homolog ASIP is a
membrane scaffolding factor required for assembly and sub-membrane attachment
of the apical PAR complex (Joberty et al.,
2000; Lin et al.,
2000
; Ebnet et al.,
2001
). The effects of the PAR complex on dlg mutant
follicle cell invasion may be exerted via a separate but
baz-dependent transmembrane adhesion complex, the nature of which is
currently unknown (Fig. 7D). In
contrast to its function during border cell migration, in humans, loss of
E-cadherin correlates with and appears to promote the occurrence of invasive
tumor formation (Birchmeier,
1995
). It has been suggested, therefore, that E-cadherins serve
distinct functions in different cell types, either by promoting or inhibiting
cell motility (Montell, 2001
).
Further studies are required to test whether the homologous proteins of Baz
(ASIP) and DaPKC (atypical PKCs iota and zeta) serve conserved functions in
mammalian cells and, in contrast to E-cadherin function, whether their loss
prevents tumor cell invasion. Moreover, it is unclear whether baz
function is restricted to the behavior of dlg mutant follicle cells
or is essential in other forms of tumor cell invasions.
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ACKNOWLEDGMENTS |
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REFERENCES |
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---|
Bilder, D., Li, M. and Perrimon, N. (2000).
Cooperative regulation of cell polarity and growth by Drosophila
tumor suppressors. Science
289,113
-116.
Birchmeier, W. (1995). E-cadherin as a tumor (invasion) suppressor gene. BioEssays 17, 97-99.[Medline]
Brower, D. L., Smith, R. J. and Wilcox, M. (1980). A monoclonal antibody specific for diploid epithelial cells in Drosophila. Nature 285,403 -405.[Medline]
Cox, D. N., Lu, B., Sun, T. Q., Williams, L. T. and Jan, Y. N. (2001a). Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr. Biol. 11,75 -87.[CrossRef][Medline]
Cox, D. N., Abdelilah-Seyfried, S., Jan, L. Y. and Jan, Y.
N. (2001b). Bazooka and atypical protein kinase C are
required to regulate oocyte differentiation in the Drosophila ovary.
Proc. Natl. Acad. Sci. USA
98,14475
-14480.
De Lorenzo, C., Strand, D. and Mechler, B. M. (1999). Requirement of Drosophila I(2)gl function for survival of the germline cells and organization of the follicle cells in a columnar epithelium during oogenesis. Int. J. Dev. Biol. 43,207 -217.[Medline]
Doe, C. Q. (2001). Cell polarity: the PARty expands. Nat. Cell Biol. 3, E7-E9.[CrossRef][Medline]
Ebnet, K., Suzuki, A., Horikoshi, Y., Hirose, T., Meyer Zu
Brickwedde, M. K., Ohno, S. and Vestweber, D. (2001). The
cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion
molecule (JAM). EMBO J.
20,3738
-3748.
Etienne-Manneville, S. and Hall, A. (2001). Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106,489 -498.[Medline]
Goode, S. and Perrimon, N. (1997). Inhibition
of patterned cell shape change and cell invasion by Discs large during
Drosophila oogenesis. Genes Dev.
11,2532
-2544.
Horne-Badovinac, S., Lin, D., Waldron, S., Schwarz, M., Mbamalu, G., Pawson, T., Jan, Y., Stainier, D. Y. and Abdelilah-Seyfried, S. (2001). Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis. Curr. Biol. 11,1492 -1502.[CrossRef][Medline]
Huynh, J. R., Petronczki, M., Knoblich, J. A. and St Johnston, D. (2001). Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila. Curr. Biol. 11,901 -906.[CrossRef][Medline]
Jacob, L., Opper, M., Metzroth, B., Phannavong, B. and Mechler, B. M. (1987). Structure of the l(2)gl gene of Drosophila and delimitation of its tumor suppressor domain. Cell 50,215 -225.[Medline]
Jan, Y. N. and Jan, L. Y. (1999). Asymmetry across species. Nat. Cell Biol. 1, E42-E44.[CrossRef][Medline]
Joberty, G., Petersen, C., Gao, L. and Macara, I. G. (2000). The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat. Cell Biol. 2, 531-539.[CrossRef][Medline]
Knoblich, J. A. (2001). Asymmetric cell division during animal development. Nat. Rev. Mol. Cell Biol. 2,11 -20.[CrossRef][Medline]
Kuchinke, U., Grawe, F. and Knust, E. (1998). Control of spindle orientation in Drosophila by the Par-3-related PDZ-domain protein Bazooka. Curr. Biol. 8,1357 -1365.[Medline]
Lin, D., Edwards, A. S., Fawcett, J. P., Mbamalu, G., Scott, J. D. and Pawson, T. (2000). A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat. Cell Biol. 2,540 -547.[CrossRef][Medline]
Mechler, B. M., McGinnis, W. and Gehring, W. J. (1985). Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J. 4,1551 -1557.[Abstract]
Montell, D. J. (2001). Command and control: regulatory pathways controlling invasive behavior of the border cells. Mech. Dev. 105,19 -25.[CrossRef][Medline]
Montell, D. J., Rørth, P. and Spradling, A. C. (1992). slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP. Cell 71, 51-62.[Medline]
Niewiadomska, P., Godt, D. and Tepass, U.
(1999). DE-Cadherin is required for intercellular motility during
Drosophila oogenesis. J. Cell Biol.
144,533
-547.
Oda, H., Uemura, T. and Takeichi, M. (1997).
Phenotypic analysis of null mutants for DE-cadherin and Armadillo in
Drosophila ovaries reveals distinct aspects of their functions in
cell adhesion and cytoskeletal organization. Genes
Cells 2,29
-40.
Patel, N. H., Snow, P. M. and Goodman, C. S. (1987). Characterization and cloning of fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila. Cell 48,975 -988.[Medline]
Peifer, M., Orsulic, S., Sweeton, D. and Wieschaus, E.
(1993). A role for the Drosophila segment polarity gene
armadillo in cell adhesion and cytoskeletal integrity during
oogenesis. Development
118,1191
-1207.
Peterson, R. T., Mably, J. D., Chen, J. N. and Fishman, M. C. (2001). Convergence of distinct pathways to heart patterning revealed by the small molecule concentramide and the mutation heart-and-soul. Curr. Biol. 11,1481 -1491.[CrossRef][Medline]
Petronczki, M. and Knoblich, J. A. (2001). DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat. Cell Biol. 3, 43-49.[CrossRef][Medline]
Rørth, P. (2002). Initiating and guiding migration: lessons from border cells. Trends Cell Biol. 12,325 -331.[CrossRef][Medline]
Spradling, A. C. (1993). Developmental genetics of oogenesis. In The Development of Drosophila melanogaster (ed. M. Bates and A. Martinez Arias), pp.1 -70. New York: Cold Spring Harbor Laboratory Press.
Tanentzapf, G., Smith, C., McGlade, J. and Tepass, U.
(2000). Apical, lateral, and basal polarization cues contribute
to the development of the follicular epithelium during Drosophila
oogenesis. J. Cell Biol.
151,891
-904.
Thiery, J. P. (2002). Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2, 442-454.[CrossRef][Medline]
Thomas, G. H. and Kiehart, D. P. (1994). Beta
heavy-spectrin has a restricted tissue and subcellular distribution during
Drosophila embryogenesis. Development
120,2039
-2050.
Thomas, G. H. and Williams, J. A. (1999).
Dynamic rearrangement of the spectrin membrane skeleton during the generation
of epithelial polarity in Drosophila. J. Cell Sci.
112,2843
-2852.
Wodarz, A., Ramrath, A., Grimm, A. and Knust, E.
(2000). Drosophila atypical protein kinase C associates
with Bazooka and controls polarity of epithelia and neuroblasts. J.
Cell Biol. 150,1361
-1374.
Woods, D. F. and Bryant, P. J. (1989). Molecular cloning of the lethal(1)discs large-1 oncogene of Drosophila. Dev. Biol. 134,222 -235.[Medline]
Woods, D. F. and Bryant, P. J. (1991). The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell 66,451 -464.[Medline]
Woods, D. F., Hough, C., Peel, D., Callaini, G. and Bryant, P. J. (1996). Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J. Cell Biol. 134,1469 -1482.[Abstract]
Woods, D. F., Wu, J. W. and Bryant, P. J. (1997). Localization of proteins to the apico-lateral junctions of Drosophila epithelia. Dev. Genet. 20,111 -118.[CrossRef][Medline]
Xu, T. and Rubin, G. M. (1993). Analysis of
genetic mosaics in developing and adult Drosophila tissues.
Development 117,1223
-1237.
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