Ecole Normale Supérieure, UMR 8542, 46, rue d'Ulm, 75230 Paris, Cedex 05, France
Author for correspondence (e-mail:
schweisg{at}wotan.ens.fr)
Accepted 16 October 2003
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SUMMARY |
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Key words: Planar cell polarity, Strabismus, Asymmetric cell division, Sensory organ
![]() |
Introduction |
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Recent studies have shed light on the mechanisms that regulate cell
polarization during asymmetric division in the Drosophila peripheral
nervous system. Each bristle sensory organ is composed of four distinct cells
that are generated from a single sensory organ precursor cell (pI for primary
precursor) via a series of stereotyped asymmetric divisions
(Fichelson and Gho, 2003;
Gho et al., 1999
;
Reddy and Rodrigues, 1999
). In
the pupal notum, the pI cell divides asymmetrically within the plane of the
single-layered epithelium, along the anteroposterior (AP) axis of the pupa, to
generate an anterior pIIb cell and a posterior pIIa cell
(Gho and Schweisguth, 1998
).
The cell-fate determinants Numb and Neuralized (Neur) localize at the anterior
cortex of the pI cell during prophase (Le
Borgne and Schweisguth, 2003
;
Rhyu et al., 1994
). At
prometaphase, the mitotic spindle rotates and lines up with these cell-fate
determinants (Bellaiche et al.,
2001a
; Roegiers et al.,
2001
). Numb and Neur co-segregate into the anterior cell, where
they both act to bias the Notch-mediated pIIa/pIIb fate decision
(Berdnik et al., 2002
;
Guo et al., 1996
;
Le Borgne and Schweisguth,
2003
; Rhyu et al.,
1994
). The anterior localization of these two cell-fate
determinants and the AP orientation of the mitotic spindle depend on the
activity of the frizzled (fz) gene
(Bellaiche et al., 2001a
;
Gho and Schweisguth, 1998
;
Roegiers et al., 2001
). In
fz mutant pupae, the division of the pI cell is oriented randomly
relative to the AP axis, with Numb localizing asymmetrically at one pole of
the mitotic spindle in most pI cells. Thus, fz activity is necessary
to orient the planar cell polarity (PCP) of the pI cell along the AP axis but
is not required for asymmetric localization of cell-fate determinants.
Fz encodes a seven-pass transmembrane receptor that signals to polarize
cells within the plane of the epithelium
(Adler, 2002). Recent studies
have indicated that Fz signaling must be spatially restricted within the cell
to ensure establishment of PCP (Strutt,
2003
; Strutt,
2002
). In pupal wing epidermal cells, which are polarized along
the proximodistal axis of the wing, Fz becomes asymmetrically localized at the
distal edge of the apical cortex of each epidermal cell
(Strutt, 2001b
). The
asymmetric distribution of Fz is regulated by PCP proteins, three of which
also localize asymmetrically. Dishevelled (Dsh) co-localizes with Fz at the
distal-apical cortex (Axelrod,
2001
; Shimada et al.,
2001
), whereas Prickle (Pk), a LIM- and PET-domain protein, and
Strabismus (Stbm; also know as Van Gogh), a four-pass transmembrane protein,
form a complex and localize opposite to Fz
(Bastock et al., 2003
;
Gubb et al., 1999
;
Jenny et al., 2003
;
Tree et al., 2002
;
Wolff and Rubin, 1998
). The
activity of each of these PCP proteins is required for each of the others to
become localized asymmetrically. Thus, formation of two opposite domains at
the apical cortex appears to be essential to spatially restrict Fz signaling
to a specific domain at one pole of the apical cortex, which, in turn, is
translated into the planar polarization of wing epidermal cells.
How Fz regulates the anterior localization of Numb and Neur as well as the
AP orientation of the spindle is not well understood. Two signaling complexes
localizing opposite to each other have, however, been implicated in this
process. The first complex includes two PDZ-containing proteins, Bazooka (Baz;
the fly homolog of Par3) and Par-6, together with the atypical Protein Kinase
C (aPKC) (for a review, see Henrique and
Schweisguth, 2003). This complex re-localizes from the apical
cortex to the posterior lateral cortex at mitosis
(Bellaiche et al., 2001b
). The
second complex includes the proteins Discs-large (Dlg), Partner of Inscuteable
(Pins) and the G
i subunit of heterotrimeric G proteins
(Bellaiche et al., 2001b
;
Schaefer et al., 2001
). This
complex localizes at the anterior lateral cortex of the dividing pI cell. The
Dlg protein contains three PDZ domains, one SH3 domain and a C-terminal GUK
domain. In epithelial cells, Dlg localizes at septate junctions and regulates
epithelial cell polarity (Bilder et al.,
2000
; Woods and Bryant,
1991
; Woods et al.,
1996
). In mitotic pI cells, Dlg interacts via its SH3 domain to
Pins and regulates the accumulation of Pins at the anterior cortex
(Bellaiche et al., 2001b
). Pins
is a modular protein with seven tetratricopeptide repeats (TPR) and three G
protein regulatory (GPR) motifs (Schaefer
et al., 2000
; Yu et al.,
2000
). The GPR motif has the ability to bind the GDP-bound form of
G
i and has been proposed to promote Gß
signaling by
dissociating the Gß
dimer from G
i·GDP
(De Vries et al., 2000
;
Schaefer et al., 2001
). The
downstream targets of the Pins-G
i, Gß
and aPKC signaling
activities in the pI cell are not known.
We have investigated the mechanisms by which PCP signaling regulates the
anterior localization of the Dlg-Pins-Gi complex during the asymmetric
pI cell division. Our data indicate that Fz localizes at the posterior cortex
prior to mitosis, whereas Stbm and Pk co-localize at the anterior cortex. At
mitosis, Stbm forms an anterior crescent that overlaps with the distribution
of Pins and Dlg, and promotes Pins cortical localization at prophase. We
propose that a read-out of PCP in the pI cell is the Stbm-dependent
localization of the Dlg-Pins-G
i complex at the anterior cortex.
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Materials and methods |
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Somatic clones were generated in: (1) Ubx-flp bazXJ106 FRT9-2/ubi-nlsGFP FRT9-2; (2) Ubx-flp dsh1 bazXJ106 FRT9-2/ubi-nlsGFP FRT9-2; and (3) Ubx-flp bazXJ106 FRT9-2/nlsGFP FRT9-2; stbm6c pupae. The Ubx-flp stock was a kind gift of J. Knoblich.
The arm Fz::GFP line is described elsewhere
(Strutt, 2001b). The
neurP72GAL4 (Bellaiche et al.,
2001a
) line was used to express Histone2B::YFP
(Bellaiche et al., 2001a
),
Pon::GFP (Lu et al., 1999a
),
tau::GFP (Kaltschmidt et al.,
2000
), Pk (Gubb et al.,
1999
), GFP::Stbm, GFP::Stbm
PBM and Stbm using the UAS/GAL4
expression system (Brand and Perrimon,
1993
). The UAS-Stbm, UAS-GFP::Stbm, UAS-GFP::Stbm
PBM,
arm-Stbm, arm-GFP::Stbm, arm-Stbm
PBM and
arm-GFP::Stbm transgenic flies were generated by P-element
transformation. In all GFP::Stbm constructs, the sequence of m6GFP (gift of A.
Brand) was fused in frame to the first codon of Stbm (the stbm cDNA
was a gift of T. Wolff). Cloning details for the UAS-GFP::Stbm,
UAS-GFP::Stbm
PBM, arm-Stbm, arm-Stbm
PBM and
arm-GFP::Stbm plasmids are available upon request.
GFP imaging
Live GFP imaging was carried out as described
(Bellaiche et al., 2001a).
Orientation of the pI cell division was measured at telophase using tau::GFP
or Pon::GFP in living pupae of the following genotypes: (1)
neurP72GAL4/UAS-tau::GFP; (2) neurP72GAL4/UAS-Pon::GFP;
(3) fzK21 UAS-tau::GFP/fzKd4a
neurP72GAL4; (4) stbm6c;
neurP72GAL4/UAS-Pon::GFP; (5) pkpk-sple14;
neurP72GAL4/UAS-Pon::GFP. For all other genotypes, the orientation
of the pI cell division was measured at telophase in fixed pupae described
previously (Bellaiche et al.,
2001a
). Localization of Pon::GFP was analyzed in: (1)
dsh1/Y; neurP72GAL4 UAS-Pon::GFP/+; (2)
stbm6c; neurP72GAL4 UAS-Pon::GFP/+; (3)
pkpk-sple14; neurP72GAL4 UAS-Pon::GFP/+; and
(4) UAS-Pk/+; neurP72GAL4 UAS-Pon::GFP/UAS-Stbm pupae.
Fluorescence Recovery After Photo-bleaching (FRAP) analysis was performed on arm-Fz::GFP pupae. Photobleaching was achieved by scanning a region of interest using the 488 nm laser source at maximal intensity.
All images were acquired on a SP2 confocal microscope and assembled using NIH image and Photoshop software.
Antibodies
Rabbit polyclonal anti-Stbm antibodies were raised against a mixture of the
two peptides CNVLAEEVVDPKSNKFV and MENESVKSEHSGRSRC.
Pupal nota were dissected and processed as previously described
(Gho et al., 1999). Primary
antibodies were: guinea pig anti-Senseless (Sens; gift from H. Bellen;
1:3000); mouse anti-Cut (2B10 obtained from the DSHB; 1:500); rat
anti-DE-Cadherin (gift from T. Uemura; 1:50); guinea pig anti-Dlg (gift from
P. Bryant; 1:3000); rabbit anti-Baz (gift from A. Wodarz; 1:3000); rabbit
anti-Pins (gift from J. Knoblich; 1:1000); rat anti-Pins (gift from P. Bryant;
1:1000); rabbit anti-Pk (gift from J. Axelrod; 1:500); rabbit anti-Stbm
(affinity-purified;1:400); and rabbit anti-GFP (Molecular Probes; 1:1000).
Cy3- and Cy5-coupled secondary antibodies were from Jackson's Laboratories and
Alexa-488-coupled secondary antibodies were from Molecular Probes.
Protein interaction assays
A cDNA fragment encompassing the intracellular domain of Stbm with
(303-584) or without (303-581) the PBM was subcloned into pGEX2KG. A PCR
product encompassing Stbm553-584 was subcloned into pGEX2KG to generate
GST-PBM. Similarly, cDNA fragments encoding the full-length DlgA isoform
(GST-Dlg) or the PDZ domains of Dlg (GST-PDZ1-3: amino acid 39-640) were
subcloned into pGEX2KG. Met 35S radiolabelled Stbm and Dlg proteins
were in vitro synthesized using the TNT kit (Promega). Stbm was synthesized in
presence of Canine Pancreatic Microsomal Membranes (Promega). Pull-down assays
were performed as previously described (beads were incubated in PBS, NP40 0.5%
and 0.5 M NaCl in the final wash) (Brou et
al., 1994).
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Results |
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|
Stbm and Pk co-localize at the apical anterior cortex of the pI cell
The stbm and pk genes not only regulate the posterior
localization of Fz::GFP in pI cells but also polarize the pI cell along the AP
axis. In stbm6c and pkpk-sple14 mutant
pupae, pI cells divided with a random orientation
(Fig. 2A,D) and Numb localized
asymmetrically but at a random position relative to the AP axis (not shown).
Thus, stbm and pk mutant pI cells exhibit planar polarity
defects that are similar to the ones previously described for fz,
dsh1 and fmi mutant pupae
(Gho and Schweisguth, 1998;
Lu et al., 1999b
).
|
We further studied the distribution of Stbm using a GFP::Stbm fusion protein. Uniform low-level expression of GFP::Stbm fully rescued the stbm6c mutant PCP phenotype (Fig. 2B), indicating that GFP::Stbm is functional (GFP::Stbm was expressed at a level similar to endogenous Stbm: see Fig. S1 at http://dev.biologists.org/supplemental). Expression of GFP::Stbm (or Stbm) in pI cells did not modify the stereotyped orientation of the pI cell division (Fig. 2C; data not shown). GFP::Stbm localized at the apical anterior cortex of the pI cell prior to division (Fig. 3A) and formed an anterior crescent at mitosis (Fig. 3B,B'). Anterior accumulation of GFP::Stbm was also seen in epidermal cells (Fig. 3C). This suggests that endogenous Stbm may also localize asymmetrically in epidermal cells but that this asymmetry is difficult to visualize because cells in the notum do not form a regular hexagonal lattice.
|
|
Overlapping distribution of Stbm, Pins and Dlg in dividing pI cells
The anterior accumulation of Stbm suggests that Stbm may co-localize with
Pins and Dlg at the anterior cortex in dividing pI cells
(Bellaiche et al., 2001b;
Schaefer et al., 2001
).
Cortical staining for Pins was first detected at prophase. Pins co-localized
with Stbm at the anterior apical cortex at this stage, whereas Dlg
predominantly accumulated at a more basal position, with only the apical-most
fraction of Dlg overlapping with Pins and Stbm
(Fig. 5A-B'''; arrowhead in
B). This suggests that Pins is first recruited at prophase at the anterior
apical cortex where Stbm and Dlg appear to overlap. At prometaphase, Stbm
localization appeared to extend to a slightly more lateral position where it
overlapped with the apical-most region of the Dlg-Pins crescent
(Fig. 5C-C''' and E-E''';
arrowhead in E; see Fig. S2 at
http://dev.biologists.org/supplemental
in order to view the complete stack). At a more basal position, high levels of
Pins and Dlg were detected anteriorly, whereas Stbm levels were very weak
(Fig. 5D-E'''). Thus, Stbm
overlapped with the apical-most part of the cortical domain containing the
Dlg-Pins complex at the anterior pole of the dividing pI cell from prophase
onwards.
|
|
Stbm promotes Pins localization at the anterior cortex at prophase
We next investigated the role of Stbm in the anterior localization of Pins.
In wild-type pupae, Pins localized at the anterior cortex of 92% of the pI
cells at prophase (n=24, Fig.
7A). By contrast, Pins localized asymmetrically in only 42% of the
pI cells in stbm6c mutant pupae at prophase
(n=17). In the remaining 58% of the pI cells, Pins was not restricted
to a single pole at the cortex and was also found in the cytoplasm
(Fig. 7B). This initial defect
in Pins localization appeared to be corrected during prometaphase as Pins
localized asymmetrically (but at a random position) in
stbm6c mutant pI cells at prometaphase
(Fig. 7E,F). These results
indicate that Stbm is required for the initial localization of Pins at the
anterior cortex.
|
Dsh excludes Pins from the posterior cortex at prophase
In contrast to the Stbm-Pk complex shown above to promote Pins cortical
localization, Dsh appears to antagonize it. In 63% of the
dsh1 mutant pI cells, Pins localized in a broad cortical
region at prophase (Fig. 7C,
n=33). This defect was rescued during prometaphase because in 75% of
the dsh1 mutant pI cells, Pins accumulated asymmetrically
(but at a random position) at prometaphase (n=28;
Fig. 7G) opposite to Baz (data
not shown). This suggests that Dsh acts antagonistically to the Pk-Stbm
complex at prophase. As Dsh acts downstream of Fz, we propose that activated
Dsh at the posterior cortex prevents Pins from accumulating there.
Dsh and Pk-Stbm act antagonistically to organize the anterior cortex
The anterior cortex has been proposed to regulate mitotic spindle
positioning. First, the anterior pole of the mitotic spindle is more tightly
associated with the anterior cortex than the posterior pole is with the
posterior cortex (Roegiers et al.,
2001). Second, in the fz mutant pI cells in which
Pon::GFP, a marker for Numb localization, is mis-partitioned into the two
daughter cells, both poles of the spindle appeared to be tightly associated
with the `anterior-like' Pon::GFP-positive cortex
(Bellaiche et al., 2001a
;
Doe, 2001
;
Roegiers et al., 2001
). It is
thought that a broadening of the `anterior-like' cortex results in the capture
of both spindle poles, hence leading to a mis-partitioning of Pon::GFP
(Fig. 8A,B). To further test
the role of Dsh, Stbm and Pk in organizing the anterior cortex, we have used
the defective partitioning of Pon::GFP as a read-out for the broadening of the
anterior domain. In wild-type pI cells, Pon::GFP was asymmetrically localized
at the anterior cortex from prophase onwards and was unequally segregated into
the anterior cell at anaphase (100%; n=54). By contrast, Pon::GFP was
mis-partitioned in 15% of fz mutant pI cells (n=33)
(Bellaiche et al., 2001a
) and
in 11% of the dsh1 mutant pI cells (n=114). Such
a defect was not seen in pkpk-sple14 mutant pupae (0%;
n=17) and was very rare in stbm6c mutant pupae
(1%; n=84). We conclude that the loss of fz or dsh
but not of pk or stbm activities leads to a broadening of
the anterior domain of the pI cell. Conversely, overexpressing Pk and Stbm
resulted in defective partitioning of Pon::GFP (16%; n=70;
Fig. 8D-E'). Moreover, a
transient extension of the Pon::GFP-positive cortical domain could also be
seen in cells that divide unequally with Pon::GFP segregating in only one of
the two cells (Fig.
8C-C''). Thus, our analysis of both Pins localization
(Fig. 7A-D) and Pon::GFP
mis-partitioning (Fig. 8)
indicate that the Pk-Stbm complex promotes the `anteriorization' of the cortex
and that Fz/Dsh signaling acts antagonistically to restrict this
`anteriorization'.
|
![]() |
Discussion |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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Recent studies have shown that Fz, Dsh, Stbm and Pk become asymmetrically
distributed during planar polarization of the wing epidermis
(Axelrod, 2001;
Bastock et al., 2003
;
Shimada et al., 2001
;
Strutt, 2001b
;
Tree et al., 2002
). In this
tissue, planar polarity is established along the proximodistal axis. Fz and
Dsh preferentially accumulate at the distal vertex of wing epidermal cells,
whereas Pk and Stbm localize at the opposite proximal pole. Planar
polarization of the eye epithelium also involves the asymmetric distribution
of Fz, Dsh, Stbm and Pk (Das et al.,
2002
; Rawls and Wolff,
2003
; Strutt et al.,
2002
; Strutt,
2002
). Thus, our analysis of the distribution of Fz, Stbm and Pk
in the pI cell reinforces the idea that unipolar distribution of PCP proteins
is a landmark of planar polarization.
Pins cortical localization as a novel read-out for PCP
Planar polarization of the pI cell occurs prior to division and is
required, upon entry into mitosis, to direct the Dlg-Pins-Gi and
Baz-Par6-aPKC complexes at the anterior and posterior cortex, respectively
(Bellaiche et al., 2001b
). We
have shown that the localization of Pins at the anterior cortex is regulated
positively by the Stbm-Pk complex and negatively by Dsh. First, loss of
stbm activity results in a delay in the cortical localization of Pins
during prophase. Second, concomitant expression of Stbm and Pk leads to a
broadening of the cortical crescent of Pins at prophase. Third, loss of
dsh PCP activity similarly results in an extended Pins crescent at
prophase. Moreover, our analysis of the defective partitioning of Pon::GFP
suggests that the Stbm-Pk complex acts antagonistically to Dsh to localize at
the anterior cortex a centrosome-attracting activity. We propose that the
Stbm-Pk complex organizes the anterior cortex and recruits the
Dlg-Pins-G
i complex as well as molecules regulating spindle
positioning.
Cortical localization of Pins is a novel read-out of PCP signaling in the
pI cell that is distinct from the ones previously identified in wing and eye
cells (Fig. 9). In wing
epidermal cells, Fz promotes the formation of a polarized actin cytoskeleton
via a pathway that possibly involves a direct interaction between Dsh and a
Daam1-Rho complex (Habas et al.,
2001) and a Rho Kinase-dependent phosphorylation of cytoplasmic
myosin (Strutt, 2001a
).
Whether Dsh also regulates microfilament assembly in pI cells remains to be
studied. In photoreceptor cells, the read-out for PCP signaling is the
transcriptional regulation of the Delta gene in R3
(Cooper and Bray, 1999
;
Das et al., 2002
;
Fanto and Mlodzik, 1999
;
Mlodzik, 1999
;
Strutt et al., 2002
). Thus,
the conserved core of PCP signaling molecules have different, cell-type
specific read-outs.
|
Maintenance of Pins anterior localization in the mitotic pI cell
Different mechanisms appear to cooperate to maintain Pins asymmetric
localization. We have shown here that baz is required for the
asymmetric localization of Pins in the absence of dsh PCP activity.
This indicates that Baz can regulate the maintenance of Pins asymmetric
localization at prometaphase. The loss of asymmetric localization of Pins in
dsh baz mutant pI cells suggests that Dsh may also contribute to
maintain Pins asymmetric localization at prometaphase. Dsh does not merely act
by excluding Stbm, a positive regulator of Pins localization in prophase,
because Pins localizes asymmetrically in baz stbm double mutant pI
cells. The mechanisms by which Baz and Dsh regulates Pins localization are not
known. However, as Pins regulates its own localization via a
Gß13F-dependent positive feedback loop
(Fuse et al., 2003;
Schaefer et al., 2001
), one
hypothesis is that Baz and/or Dsh negatively regulates Gß13F signaling
activity.
Implications for the read-out of PCP in vertebrates
One of the best examples of PCP in mammals is the stereotyped planar
orientation of the stereociliary bundles that are located at the apical cortex
of each mechanosensory hair cells within the cochlea. In these cells, the
first sign of polarization is the stereotyped movement, at the luminal surface
of the cell and along the neural-abneural axis, of the kinocilium, the single
tubulin-based cilium, from the center towards the abneural pole of the cell
(Montcouquiol et al., 2003).
Recently, a mutation in a stbm homolog, Vangl2, has been
shown to result in the defective orientation of the stereociliary bundles.
This planar cell polarity defect appears to result from the randomly oriented
center-to-periphery movement of the kinocilium
(Montcouquiol et al., 2003
).
Because LGN, a mammalian homolog of Pins
(Yu et al., 2003
), is known to
regulate microtubule stability (Du et al.,
2002
), it is tempting to speculate that Vangl2 may regulate via
LGN a microtubule-dependent process regulating kinocilium movement along the
neural-abneural axis. Future studies will reveal whether the regulation of
Pins/LGN cortical localization is a conserved read-out of PCP.
Note added in proof
A recent study by Lee et al. (Lee et
al., 2003) indicates that Stbm directly interacts with Dlg via its
C-terminal PBM. Dlg and Stbm can be co-immunoprecipated from a
Drosophila embryonic extract. This direct interaction was also
observed with mammalian homologs of Stbm and Dlg. The authors propose that the
Dlg-Stbm interaction is important for the formation of new plasma membrane
during cellularisation of the Drosophila embryo.
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
Footnotes |
---|
* Present address: Institut Curie, UMR 144, 12 rue Lhomond, 75005 Paris,
France
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adler, P. N. (2002). Planar signaling and morphogenesis in Drosophila. Dev. Cell 2, 525-535.[Medline]
Axelrod, J. D. (2001). Unipolar membrane
association of Dishevelled mediates Frizzled planar cell polarity signaling.
Genes Dev. 15,1182
-1187.
Bastock, R., Strutt, H. and Strutt, D. (2003).
Strabismus is asymmetrically localised and binds to Prickle and Dishevelled
during Drosophila planar polarity patterning.
Development 130,3007
-3014.
Bellaiche, Y., Gho, M., Kaltschmidt, J. A., Brand, A. H. and Schweisguth, F. (2001a). Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division. Nat. Cell Biol. 3, 50-57.[CrossRef][Medline]
Bellaiche, Y., Radovic, A., Woods, D. F., Hough, C. D., Parmentier, M. L., O'Kane, C. J., Bryant, P. J. and Schweisguth, F. (2001b). The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Cell 106,355 -366.[Medline]
Berdnik, D., Torok, T., Gonzalez-Gaitan, M. and Knoblich, J. (2002). The endocytic protein alpha-adaptin is required for Numb-mediated asymmetric cell division in Drosophila. Dev. Cell 3,221 .[Medline]
Bilder, D., Li, M. and Perrimon, N. (2000).
Cooperative regulation of cell polarity and growth by Drosophila tumor
suppressors. Science
289,113
-116.
Brand, A. H. and Perrimon, N. (1993). Targeted
gene expression as a means of altering cell fates and generating dominant
phenotypes. Development
118,401
-415.
Brou, C., Logeat, F., Lecourtois, M., Vandekerckhove, J., Kourilsky, P., Schweisguth, F. and Israel, A. (1994). Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless. Genes Dev. 8,2491 -2503.[Abstract]
Cooper, M. T. and Bray, S. J. (1999). Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature 397,526 -530.[CrossRef][Medline]
Das, G., Reynolds-Kenneally, J. and Mlodzik, M. (2002). The atypical cadherin Flamingo links Frizzled and Notch signaling in planar polarity establishment in the Drosophila eye. Dev. Cell 2,655 -666.[Medline]
De Vries, L., Fischer, T., Tronchere, H., Brothers, G. M.,
Strockbine, B., Siderovski, D. P. and Farquhar, M. G. (2000).
Activator of G protein signaling 3 is a guanine dissociation inhibitor for
galpha i subunits. Proc. Natl. Acad. Sci. USA
97,14364
-14369.
Doe, C. Q. (2001). Cell polarity: the PARty expands. Nat. Cell Biol. 3, E7-E9.[CrossRef][Medline]
Du, Q., Taylor, L., Compton, D. A. and Macara, I. G. (2002). LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr. Biol. 12,1928 -1933.[CrossRef][Medline]
Fanto, M. and Mlodzik, M. (1999). Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye. Nature 397,523 -526.[CrossRef][Medline]
Fichelson, P. and Gho, M. (2003). The glial
cell undergoes apoptosis in the microchaete lineage of Drosophila.
Development 130,123
-133.
Fuse, N., Hisata, K., Katzen, A. L. and Matsuzaki, F. (2003). Heterotrimeric g proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions. Curr. Biol. 13,947 -954.[CrossRef][Medline]
Gho, M. and Schweisguth, F. (1998). Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393,178 -181.[CrossRef][Medline]
Gho, M., Bellaiche, Y. and Schweisguth, F.
(1999). Revisiting the Drosophila microchaete lineage: a novel
intrinsically asymmetric cell division generates a glial cell.
Development 126,3573
-3584.
Gubb, D., Green, C., Huen, D., Coulson, D., Johnson, G., Tree,
D., Collier, S. and Roote, J. (1999). The balance between
isoforms of the prickle LIM domain protein is critical for planar polarity in
Drosophila imaginal discs. Genes Dev.
13,2315
-2327.
Guo, M., Jan, L. Y. and Jan, Y. N. (1996). Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Neuron 17,27 -41.[Medline]
Habas, R., Kato, Y. and He, X. (2001). Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 107,843 -854.[CrossRef][Medline]
Henrique, D. and Schweisguth, F. (2003). Cell polarity: the ups and downs of the Par6/aPKC complex. Curr. Opin. Genet. Dev. 13,341 -350.[CrossRef][Medline]
Jenny, A., Darken, R. S., Wilson, P. A. and Mlodzik, M.
(2003). Prickle and Strabismus form a functional complex to
generate a correct axis during planar cell polarity signaling. EMBO
J. 22,4409
-4420.
Kaltschmidt, J. A., Davidson, C. M., Brown, N. H. and Brand, A. H. (2000). Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system. Nat. Cell Biol. 2,7 -12.[CrossRef][Medline]
Le Borgne, R. and Schweisguth, F. (2003). Unequal segregation of Neuralized biases Notch activation during asymmetric cell division. Dev. Cell 5, 139-148.[Medline]
Lee, O. K., Frese, K. K., James, J. S., Chadda, D., Chen, Z. H., Javier, R. T. and Cho, K. O. (2003). Discs-Large and Strabismus are functionally linked to plasma membrane formation. Nat. Cell Biol. 5,987 -993.[CrossRef][Medline]
Lu, B., Ackerman, L., Jan, L. Y. and Jan, Y.-N. (1999a). Modes of protein movement that lead to the asymmetric localization of Partner of Numb during Drosophila neuroblast division. Mol. Cell 4,883 -891.[Medline]
Lu, B., Usui, T., Uemura, T., Jan, L. and Jan, Y. N. (1999b). Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila. Curr. Biol. 9,1247 -1250.[CrossRef][Medline]
Mlodzik, M. (1999). Planar polarity in the
Drosophila eye: a multifaceted view of signaling specificity and cross-talk.
EMBO J. 18,6873
-6879.
Montcouquiol, M., Rachel, R. A., Lanford, P. J., Copeland, N. G., Jenkins, N. A. and Kelley, M. W. (2003). Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423,173 -177.[CrossRef][Medline]
Rawls, A. S. and Wolff, T. (2003). Strabismus
requires Flamingo and Prickle function to regulate tissue polarity in the
Drosophila eye. Development
130,1877
-1887.
Reddy, G. V. and Rodrigues, V. (1999). A glial
cell arises from an additional division within the mechanosensory lineage
during development of the microchaete on the Drosophila notum.
Development 126,4617
-4622.
Rhyu, M. S., Jan, L. Y. and Jan, Y. N. (1994). Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. Cell 76,477 -491.[Medline]
Roegiers, F., Younger-Shepherd, S., Jan, L. Y. and Jan, Y. N. (2001). Two types of asymmetric divisions in the Drosophila sensory organ precursor cell lineage. Nat. Cell Biol. 3,58 -67.[CrossRef][Medline]
Schaefer, M., Shevchenko, A. and Knoblich, J. A. (2000). A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr. Biol. 10,353 -362.[CrossRef][Medline]
Schaefer, M., Petronczki, M., Dorner, D., Forte, M. and Knoblich, J. A. (2001). Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107,183 -194.[Medline]
Shimada, Y., Usui, T., Yanagawa, S., Takeichi, M. and Uemura, T. (2001). Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization. Curr. Biol. 11,859 -863.[CrossRef][Medline]
Strutt, D. (2001a). Planar polarity: getting ready to ROCK. Curr. Biol. 11,R506 -R509.[CrossRef][Medline]
Strutt, D. I. (2001b). Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. Mol. Cell 7,367 -375.[Medline]
Strutt, D. I. (2002). The asymmetric subcellular localisation of components of the planar polarity pathway. Semin. Cell Dev. Biol. 13,225 -231.[CrossRef][Medline]
Strutt, D. (2003). Frizzled signalling and cell
polarisation in Drosophila and vertebrates.
Development 130,4501
-4513.
Strutt, D., Johnson, R., Cooper, K. and Bray, S. (2002). Asymmetric localization of frizzled and the determination of notch-dependent cell fate in the Drosophila eye. Curr. Biol. 12,813 -824.[CrossRef][Medline]
Tree, D. R., Shulman, J. M., Rousset, R., Scott, M. P., Gubb, D. and Axelrod, J. D. (2002). Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell 109,371 -381.[Medline]
Wolff, T. and Rubin, G. M. (1998). Strabismus,
a novel gene that regulates tissue polarity and cell fate decisions in
Drosophila. Development
125,1149
-1159.
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]
Yu, F., Morin, X., Cai, Y., Yang, X. and Chia, W. (2000). Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 100,399 -409.[Medline]
Yu, F., Morin, X., Kaushik, R., Bahri, S., Yang, X. and Chia,
W. (2003). A mouse homologue of Drosophila pins can
asymmetrically localize and substitute for pins function in Drosophila
neuroblasts. J. Cell Sci.
116,887
-896.