Drosophila Frizzled-2 (Dfz2) has been identified as a putative fly Wingless (Wg) receptor. Although Dfz2 shows significant homology with Fz, a protein that operates in the mechanisms that establish planar polarity in Drosophila epithelia, any clear evidence for an involvement by Fz in a Wnt signaling pathway has hitherto been absent. Here we describe the planar polarity phenotypes of loss-of-function and overexpression of Fz in the developing Drosophila eye and find it almost identical to the loss-of-function or overexpression of Dishevelled (Dsh - a protein operating in Wnt second messenger systems). In addition, we show that overexpression of Shaggy (Sgg - another component of the Wnt pathway) in the eye also causes a phenotype similar to Fz and Dsh. To test further the link between planar polarity and Wnt signaling we misexpressed Wg in the developing eye and found it had a potent polarizing effect in the retinal epithelium. Since the overexpression of Fz in the developing eye gave a phenotype consistent with activating the Wnt pathway, we tested overexpression of Fz in the developing embryonic ectoderm and found that it phenocopied overexpression of Wg. To check that Fz was indeed able to activate a Wnt pathway we overexpressed it in Drosophila tissue culture cells and observed the characteristic phosphorylation of Dsh that occurs in response to Wnt signaling. Taken together our results significantly strengthen the case for Fz acting in a Wnt signaling pathway in Drosophila.

REFERENCES

Axelrod
J. D.
,
Matsuno
K.
,
Artavanis-Tsakonis
S.
,
Perrimon
N.
(
1996
)
Interaction between wingless and Notch signaling pathways mediated by dishevelled.
Science
271
,
1826
1832
Baker
N. E.
(
1987
)
Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos.
EMBO J
6
,
1765
1773
Baker
N. E.
(
1988
)
Embryonic and imaginal requirements for wingless, a segment-polarity gene in Drosophila.
Dev. Biol
125
,
96
108
Basler
K.
,
Christen
B.
,
Hafen
E.d.
(
1991
)
Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the Developing Drosophila eye.
Cell
64
,
1069
1081
Bejsovec
A.
,
Martinez-Arias
A.
(
1991
)
Roles of wingless in patterning the larval epidermis of Drosophila.
Development
113
,
471
486
Bhanot
P.
,
Brink
M.
,
Harryman Samos
C.
,
Hsieh
J.-C.
,
Wang
Y.
,
Macke
J. P.
,
Andrew
D.
,
Nathans
J.
,
Nusse
R.
(
1996
)
A new member of the frizzled family from Drosophila functions as a wingless receptor.
Nature
382
,
225
230
Couso
J. P.
,
Martinez-Arias
A.
(
1994
)
Notch is required for wingless signaling in the epidermis of Drosophila.
Cell
79
,
259
272
Dougan
S. T.
,
DiNardo
S.
(
1992
)
wingless generates cell type diversity among engrailed expressing cells.
Nature
360
,
347
350
Heemskerk
J.
,
DiNardo
S.
,
Kostriken
R.
,
O'Farrell
P. H.
(
1991
)
Multiple modes of engrailed regulation in the progression towards cell fate determination.
Nature
352
,
404
410
Jones
K. J.
,
Liu
J.
,
Adler
P. N.
(
1996
)
Molecular analysis of EMS-induced frizzled mutations in Drosophila melanogaster.
Genetics
142
,
205
215
Koelle
M. R.
,
Talbot
W. S.
,
Seagraves
W. A.
,
Bender
M. T.
,
Cherbas
P.
,
Hogness
D. S.
(
1991
)
The DrosophilaEcR gene encodes an ecdysone receptor, a new family member of the steroid receptor superfamily.
Cell
67
,
59
77
Krasnow
R. E.
,
Adler
P. A.
(
1994
)
A single frizzled protein has a dual function in tissue polarity.
Development
120
,
1883
1893
Lawrence
P. A.
(
1966
)
Gradients in the insect segment: The orientation of hairs in the milkweed bug Oncopeltus fasciatus.
J. Exp. Biol
44
,
607
620
Leeuwen
F.
,
van, Samos
C. H.
,
Nusse
R.
(
1994
)
Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cells.
Nature
368
,
342
344
Ma
C.
,
Moses
K.
(
1995
)
wingless and patched are negative regulators of the morphogenetic furrow and can affect polarity in the developing Drosophila compound eye.
Development
121
,
2279
2289
Meer
S. V. D.
(
1977
)
Optical clean and permanent whole preparation for phase contrast microscopy of cuticular structures of insect larvae.
Dros. Inf. Service
52
,
160
161
Noordermeer
J.
,
Johnston
P.
,
Rijsewuk
,
Nusse
R.
,
Lawrence
P. A.
(
1992
)
The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo.
Development
116
,
711
719
Noordermeer
J.
,
Klingensmith
J.
,
Perrimon
N.
,
Nusse
R.
(
1994
)
Dishevelled and armadillo act in the wingless signaling pathway in Drosophila.
Nature
367
,
80
83
Rijsewijk
F.
,
Schuermann
M.
,
Wagenaar
E.
,
Parren
P.
,
Weigel
D.
,
Nusse
R.
(
1987
)
The Drosophila homolog of the mouse mammmary oncogene int-1 is identical to the segment polarity gene wingless.
Cell
50
,
649
657
Siegfried
E.
,
Chou
T.
,
Perrimon
N.
(
1992
)
Wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate.
Cell
71
,
1167
1179
Siegfried
E.
,
Wilder
E.
,
Perrimon
N.
(
1994
)
Components of wingless signalling in Drosophila.
Nature
367
,
76
80
Struhl
G.
,
Barbash
D. A.
,
Lawrence
P. A.
(
1997
)
Hedgehog acts by distinct gradient and signal relay mechanisms to organise cell type and cell polarity in the Drosophila abdomen.
Development
124
,
2155
2165
Struhl
G.
,
Basler
K.
(
1993
)
Organizing activity of wingless protein in Drosophila.
Cell
72
,
527
540
Stumpf
H. F.
(
1967
)
Über den Verlauf eines schuppenorientierenden Gefalles bei Galleria mellonella.
Wilhelm Roux's Arch. EntwMech. Org.
158
315
330
Thiesen
H.
,
Purcell
J.
,
Bennet
M.
,
Kansgara
D.
,
Syed
A.
,
Marsh
J. L.
(
1994
).
dishevelled is required during wingless signaling to establish both cell polarity and cell identity.
Development
120
,
347
360
Tomlinson
A.
,
Ready
D. F.
(
1987
)
Cell fate in the Drosophila ommatidium.
Dev. Biol
123
,
264
275
Treisman
J. E.
,
Rubin
G. M.
(
1995
)
wingless inhibits morphogenetic furrow movement in the Drosophila eye disc.
Development
121
,
3519
3527
Vinson
C.
,
Adler
P. N.
(
1987
)
Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila.
Nature
329
,
549
551
Vinson
C. R.
,
Conover
S.
,
Adler
P. N.
(
1989
)
A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domain.
Nature
338
,
263
264
Wang
Y.
,
Macke
J. P.
,
Abella
B. J.
,
Andreasson
K.
,
Worley
P.
,
Gilbert
D. J.
,
copeland
N. G.
,
Jenkins
N. A.
,
Nathans
J.
(
1996
)
A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled.
J. Biol. Chem
271
,
4468
4476
Wehrli
M.
,
Tomlinson
A.
(
1995
)
Epithelial planar polarity in the developing Drosophila eye.
Development
121
,
2451
2459
Yanagawa
S.
,
Leeuwen
F.
,
van, Wodarz
A.
,
Klingensmith
J.
,
Nusse
R.
(
1995
)
The dishevelled protein is modified by wingless signaling in Drosophila.
Genes Dev
9
,
1087
1097
Zheng
L.
,
Zhang
J.
,
Carthew
R. W.
(
1995
)
frizzled regulates mirror-symmetric pattern formation in the Drosophila eye.
Development
121
,
3045
3055
This content is only available via PDF.