Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997–4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.

REFERENCES

Adler
P. N.
(
1992
)
The genetic control of tissue polarity in Drosophila.
BioEssays
14
,
735
741
Amores
A.
,
Force
A.
,
Yan
Y. L.
,
Joly
L.
,
Amemiya
C.
,
Fritz
A.
,
Ho
R. K.
,
Langeland
J.
,
Prince
V.
,
Wang
Y. L.
(
1998
)
Zebrafish hox clusters and vertebrate genome evolution.
Science
282
,
1711
1714
Axelrod
J. D.
,
Miller
J. R.
,
Shulman
J. M.
,
Moon
R. T.
,
Perrimon
N.
(
1998
)
Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.
Genes Dev
12
,
2610
2622
Barrett
K.
,
Leptin
M.
,
Settleman
J.
(
1997
)
The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation.
Cell
91
,
905
915
Blumberg
B.
,
Wright
C. V. E.
,
De Robertis
E. M.
,
Cho
K. W. Y.
(
1991
)
Organizer-specific homeobox genes in Xenopus laevis embryos.
Science
253
,
194
196
Boutros
M.
,
Mlodzik
M.
(
1999
)
Dishevelled: at the crossroads of divergent intracellular signaling pathways.
Mech. Dev
83
,
27
37
Boutros
M.
,
Paricio
N.
,
Strutt
D. I.
,
Mlodzik
M.
(
1998
)
Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.
Cell
94
,
109
118
Brannon
M.
,
Gomperts
M.
,
Sumoy
L.
,
Moon
R. T.
,
Kimelman
D.
(
1997
)
A-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus.
Genes Dev
11
,
2359
2370
Brieher
W. M.
,
Gumbiner
B. M.
(
1994
)
Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps.
J. Cell Biol
126
,
519
527
Cadigan
K. M.
,
Nusse
R.
(
1997
)
Wnt signaling: a common theme in animal development.
Genes Dev
11
,
3286
3305
Casey
E. S.
,
Tada
M.
,
Fairclough
L.
,
Wylie
C. C.
,
Heasman
J.
,
Smith
J. C.
(
1999
)
Bix4 is activated by VegT and mediates endoderm formation in Xenopus development.
Development
126
,
4193
4200
Christian
J. L.
,
McMahon
J. A.
,
McMahon
A. P.
,
Moon
R. T.
(
1991
)
Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing factors, may play a role in ventral mesodermal patterning during embryogenesis.
Development
111
,
1045
1055
Conlon
F. L.
,
Sedgwick
S. G.
,
Weston
K. M.
,
Smith
J. C.
(
1996
)
Inhibition of Xbra transcription activation causes defects in mesodermalpatterning and reveals autoregulation of Xbra in dorsal mesoderm.
Development
122
,
2427
2435
Conlon
F. L.
,
Smith
J. C.
(
1999
)
Interference with Brachyury function inhibits convergent extension, causes apoptosis, and reveals separate requirements in the FGF and activin signalling pathways.
Dev. Biol
213
,
85
100
Cooke
J.
,
Smith
J. C.
,
Smith
E. J.
,
Yaqoob
M.
(
1987
)
The organization of mesodermal pattern in Xenopus laevis: experiments using a Xenopus mesoderm-inducing factor.
Development
101
,
893
908
Cunliffe
V.
,
Smith
J. C.
(
1992
)
Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue.
Nature
358
,
427
430
Cunliffe
V.
,
Smith
J. C.
(
1994
)
Specification of mesodermal pattern in Xenopus laevis by interactions between Brachyury, noggin and Xwnt-8.
EMBO J
13
,
349
359
Deardorff
M. A.
,
Tan
C.
,
Conrad
L. J.
,
Klein
P. S.
(
1998
)
Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.
Development
125
,
2687
2700
Du
J. S.
,
Purcell
S. M.
,
Christian
J. L.
,
McGrew
L. L.
,
Moon
R. T.
(
1995
)
Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
Mol. Cell. Biol
15
,
2625
2634
Fagotto
F.
,
Guger
K.
,
Gumbiner
B. M.
(
1997
)
Induction of the primary dorsalizing center in Xenopus by the Wnt/GSK/beta-catenin signaling pathway, but not by Vg1, Activin or Noggin.
Development
124
,
453
460
Gawantka
V.
,
Delius
H.
,
Hirschfeld
K.
,
Blumenstock
C.
,
Niehrs
C.
(
1995
)
Antagonizing the Spemann organizer: role of the homeobox gene Xvent-1.
EMBO J
14
,
6268
6279
Glinka
A.
,
Delius
H.
,
Blumenstock
C.
,
Niehrs
C.
(
1996
)
Combinatorial signalling by Xwnt11 and Xnr3 in the organizer epithelium.
Mech. Dev
60
,
221
231
Griffin
K. J.
,
Amacher
S. L.
,
Kimmel
C. B.
,
Kimelman
D.
(
1998
)
Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes.
Development
125
,
3379
3388
Harland
R. M.
(
1991
)
In situ hybridization: an improved whole mount method for Xenopus embryos.
Meth. Cell Biol
36
,
675
685
Herrmann
B. G.
,
Labeit
S.
,
Poutska
A.
,
King
T. R.
,
Lehrach
H.
(
1990
)
Cloning of the T gene required in mesoderm formation in the mouse.
Nature
343
,
617
622
Hoppler
S.
,
Brown
J. D.
,
Moon
R. T.
(
1996
)
Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos.
Genes Dev
10
,
2805
2817
Hopwood
N. D.
,
Pluck
A.
,
Gurdon
J. B.
(
1989
)
MyoD expression in the forming somites is an early response to mesoderm induction in Xenopus embryos.
Embo J
8
,
3409
3417
Hopwood
N. D.
,
Pluck
A.
,
Gurdon
J. B.
(
1991
)
Xenopus Myf-5 marks early muscle cells and can activate muscle genes ectopically in early embryos.
Development
111
,
551
560
Horb
M. E.
,
Thomsen
G. H.
(
1997
)
A vegetally-localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation.
Development
124
,
1689
1698
Isaacs
H. V.
,
Pownall
M. E.
,
Slack
J. M. W.
(
1994
)
eFGF regulates Xbra expression during Xenopus gastrulation.
EMBO J
13
,
4469
4481
Isaacs
H. V.
,
Tannahill
D.
,
Slack
J. M. W.
(
1992
)
Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification.
Development
114
,
711
720
Itoh
K.
,
Sokol
S. Y.
(
1997
)
Graded amounts of Xenopus dishevelled specify discrete anteroposterior cell fates in prospective ectoderm.
Mech. Dev
61
,
113
125
Kim
S.-H.
,
Yamamoto
A.
,
Bouwmeester
T.
,
Agius
E.
,
De Robertis
E. M.
(
1998
)
The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation.
Development
125
,
4681
4691
Kintner
C. R.
,
Brockes
J. P.
(
1984
)
Monoclonal antibodies recognise blastemal cells derived from differentiating muscle in newt limb regeneration.
Nature
308
,
67
69
Kishida
S.
,
Yamamoto
H.
,
Hino
S.
,
Ikeda
S.
,
Kishida
M.
,
Kikuchi
A.
(
1999
)
DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
Mol. Cell. Biol
19
,
4414
4422
Kispert
A.
,
Korschorz
B.
,
Herrmann
B. G.
(
1995
)
The T protein encoded by Brachyury is a tissue-specific transcription factor.
EMBO J
14
,
4763
4772
Krasnow
R. E.
,
Adler
P. N.
(
1994
)
A single frizzled protein has a dual function in tissue polarity.
Development
120
,
1883
1893
Ku
M.
,
Melton
D. A.
(
1993
)
Xwnt-11, a maternally expressed Xenopus wnt gene.
Development
119
,
1161
1173
Lemaire
P.
,
Garrett
N.
,
Gurdon
J. B.
(
1995
)
Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal vegetal cells of blastulae and able to induce a complete secondary axis.
Cell
81
,
85
94
Li
L.
,
Yuan
H.
,
Xie
W.
,
Mao
J.
,
Caruso
A. M.
,
Sussman
D. J.
,
Wu
D.
(
1999
)
Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells.
J. Biol. Chem
274
,
129
134
Lustig
K. D.
,
Kroll
K. L.
,
Sun
E. E.
,
Kirschner
M. W.
(
1996
)
Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation.
Development
122
,
4001
4012
Mohun
T. J.
,
Brennan
S.
,
Dathan
N.
,
Fairman
S.
,
Gurdon
J. B.
(
1984
)
Cell type-specific activation of actin genes in the early amphibian embryo.
Nature
311
,
716
721
Molenaar
M.
,
van de Wetering
M.
,
Oosterwegel
M.
,
Peter-Maduro
J.
,
Godsave
S.
,
Korinek
V.
,
Roose
J.
,
Destree
O.
,
Clevers
H.
(
1996
)
XTcf-3 transcription factor mediates-catenin-induced axis formation in Xenopus embryos.
Cell
86
,
391
399
Moon
R. T.
,
Campbell
R. M.
,
Christian
J. L.
,
McGrew
L. L.
,
Shih
J.
,
Fraser
S.
(
1993
)
Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.
Development
119
,
97
111
Morgan
R.
,
Hooiveld
M. H. W.
,
In der Rieden
P.
,
Durston
A. J.
(
1999
)
A conserved 30 base pair element in the Wnt-5a promoter is sufficient both to drive its early embryonic expression and to mediate its repression by otx2.
Mech. Dev
85
,
97
102
O'Reilly
M.-A. J.
,
Smith
J. C.
,
Cunliffe
V.
(
1995
)
Patterning of the mesoderm in Xenopus: dose-dependent and synergistic effects of Brachyury and Pintallavis.
Development
121
,
1351
1359
Ponting
C. P.
,
Bork
P.
(
1996
)
Pleckstrin's repeat performance: a novel domain in G-protein signaling?.
Trends Biochem. Sci
21
,
245
246
Ponting
C. P.
,
Phillips
C.
,
Davies
K. E.
,
Blake
D. J.
(
1997
)
PDZ domains: targeting signalling molecules to sub-membranous sites.
BioEssays
19
,
469
479
Sasai
Y.
,
Lu
B.
,
Steinbeisser
H.
,
Geisssert
D.
,
Gont
L. K.
,
De Robertis
E. M.
(
1994
)
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
Cell
79
,
779
790
Schulte-Merker
S.
,
Smith
J. C.
(
1995
)
Mesoderm formation in response to Brachyury requires FGF signalling.
Curr. Biol
5
,
62
67
Schulte-Merker
S.
,
van Eeden
F. M.
,
Halpern
M. E.
,
Kimmel
C. B.
,
Nusslein-Volhard
C.
(
1994
)
No tail (ntl) is the zebrafish homologue of the mouse T (Brachyury) gene.
Development
120
,
1009
1015
Sheldahl
L. C.
,
Park
M.
,
Malbon
C. C.
,
Moon
R. T.
(
1999
)
Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner.
Curr. Biol
9
,
695
698
Shih
J.
,
Keller
R.
(
1992
)
Cell motility driving mediolateral intercalation in explants of Xenopus laevis.
Development
116
,
901
914
Slusarski
D. C.
,
Corces
V. G.
,
Moon
R. T.
(
1997
)
Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.
Nature
390
,
410
413
Smith
J. C.
,
Price
B. M. J.
,
Green
J. B. A.
,
Weigel
D.
,
Herrmann
B. G.
(
1991
)
Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction.
Cell
67
,
79
87
Smith
J. C.
,
Symes
K.
,
Hynes
R. O.
,
DeSimone
D.
(
1990
)
Mesoderm induction and the control of gastrulation in Xenopus laevis: the roles of fibronectin and integrins.
Development
108
,
289
298
Smith
J. C.
,
Watt
F. M.
(
1985
)
Biochemical specificity of Xenopus notochord.
Differentiation
29
,
109
115
Sokol
S. Y.
(
1996
)
Analysis of Dishevelled signalling pathways during Xenopus development.
Curr. Biol
6
,
1456
1467
Sokol
S. Y.
,
Klingensmith
J.
,
Perrimon
N.
,
Itoh
K.
(
1995
)
Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled.
Development
121
,
1637
1647
Stennard
F.
,
Carnac
G.
,
Gurdon
J. B.
(
1996
)
The Xenopus T-box gene, Antipodean, encodes a vegetally localised maternal mRNA and can trigger mesoderm formation.
Development
122
,
4179
4188
Strutt
D. I.
,
Weber
U.
,
Mlodzik
M.
(
1997
)
The role of RhoA in tissue polarity and Frizzled signalling.
Nature
387
,
292
295
Symes
K.
,
Smith
J. C.
(
1987
)
Gastrulation movements provide an early marker of mesoderm induction in Xenopus.
Development
101
,
339
349
Tada
M.
,
Casey
E.
,
Fairclough
L.
,
Smith
J. C.
(
1998
)
Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm.
Development
125
,
3997
4006
Tada
M.
,
O'Reilly
M.-A. J.
,
Smith
J. C.
(
1997
)
Analysis of competence and of Brachyury autoinduction by use of hormone-inducible Xbra.
Development
124
,
2225
2234
Torres
M. A.
,
Yang-Snyder
J. A.
,
Purcell
S. M.
,
DeMarais
A. A.
,
McGrew
L. L.
,
Moon
R. T.
(
1996
)
Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
J. Cell Biol
133
,
1123
1137
Wilson
P.
,
Keller
R.
(
1991
)
Cell rearrangement during gastrulation of Xenopus: direct observation of cultured explants.
Development
112
,
289
300
Wilson
V.
,
Manson
L.
,
Skarnes
W. C.
,
Beddington
R. S. P.
(
1995
)
The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation.
Development
121
,
877
886
Yanagawa
S.
,
van Leeuwen
F.
,
Wodarz
A.
,
Klingensmith
J.
,
Nusse
R.
(
1995
)
The Dishevelled protein is modified by Wingless signaling in Drosophila.
Genes Dev
9
,
1087
1097
Zhang
J.
,
King
M. L.
(
1996
)
Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning.
Development
122
,
4119
4129
Zhong
Y.
,
Brieher
W. M.
,
Gumbiner
B. M.
(
1999
)
Analysis of C-cadherin regulation during tissue morphogenesis with an activating antibody.
J. Cell Biol
144
,
351
359
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