The Spemann organizer induces neural tissue, dorsalizes mesoderm and generates a second dorsal axis. We report the isolation and characterization of Smad10, which has all three of these Spemann activities. Smad10 is expressed at the appropriate time to transduce Spemann signals endogenously. Like the organizer, Smad10 generates anterior and posterior neural tissues. Smad10 appears to function downstream of the Spemann organizer, consistent with a role in mediating organizer-derived signals. Interestingly, Smad10, unlike previously characterized mediators of Spemann activity, does not appear to block BMP signals. This finding, coupled with the functional activity and expression profile, suggests that Smad10 mediates Spemann action in a novel manner.

Reference

Bouwmeester
T.
,
Kim
S.
,
Sasai
Y.
,
Lu
B.
,
De Robertis
E. M.
(
1996
)
Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer.
Nature
382
,
595
601
Bradley
L.
,
Snape
A.
,
Bhatt
S.
,
Wilkinson
D.
(
1993
)
The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest.
Mech. Dev
40
,
73
84
Candia
A. F.
,
Watabe
T.
,
Hawley
S. H. B.
,
Onichtchouk
D.
,
Zhng
Y.
,
Derynck
R.
,
Niehrs
C.
,
Cho
K. W. Y.
(
1997
)
Cellular interpretation of multiple TGF-signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads.
Development
124
,
4467
4480
Carnac
G.
,
Kodjabachian
L.
,
Gurdon Lemaire
P.
(
1996
)
The homeobox gene Siamois is a target of the Wnt dorsalization pathway andtriggers organizer activity in the absence of mesoderm.
Development
122
,
3055
3056
Cho
K.
,
Blumberg
B.
,
Steinbeisser
H.
,
De Robertis
E.
(
1991
)
Molecular nature of Spemann's organizer: the role of Xenopus homeobox gene goosecoid.
Cell
67
,
1111
1120
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
1056
Cox
W.
,
Hemmati-Brivanlou
A.
(
1995
)
Caudalization of neural fate by tissue recombination and bFGF.
Development
121
,
4349
4358
Darras
S.
,
Marikawa
Y.
,
Elinson
R.
,
Lemaire
P.
(
1997
)
Animal and vegetal pole cells of early Xenopus embryos respond differently to maternal dorsal determinants: implications for the patterning of the organizer.
Development
124
,
4275
4286
Derynck
R.
,
Zhang
Y.
(
1996
)
Intracellular signaling: The Mad way to do it.
Current Biology
6
,
1226
1229
Eppert
K.
,
Scherer
S.
,
Ozcelik
H.
,
Pirone
R.
,
Hoodless
P.
,
Kim
H.
,
Tsui
L. C.
,
Bapat
B.
,
Gallinger
S.
,
Andrulis
I.
,
Thomsen
G.
,
Wrana
J.
,
Attisano
L.
(
1996
)
MADR2 maps to 18q21 and encodes a TGF-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
Cell
88
,
543
552
Gawantka
V.
,
Delius
H.
,
Hirschfeld
K.
,
Blumenstock
C.
,
Niehrs
C.
(
1995
)
Antagonizing the Spemman organizer: role of the homeobox gene Xvent.
EMBO J
14
,
6268
6279
Graff
J.
,
Thies
R.
,
Song
J.
,
Celeste
A.
,
Melton
D.
(
1994
)
Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo.
Cell
79
,
169
179
Graff
J.
,
Bansal
A.
,
Melton
D.
(
1996
)
Xenopus Mad proteins transduce distinct subsets of signals for the TGFsuperfamily.
Cell
85
,
479
487
Graff
J.
(
1997
)
Embryonic patterning: To BMP or not to BMP that is the question.
Cell
89
,
171
174
Hansen
C.
,
Marion
C.
,
Steele
K.
,
George
S.
,
Smith
W.
(
1997
)
Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3.
Development
124
,
483
492
Hayashi
H.
,
Abdollah
S.
,
Qiu
Y.
,
Cai
J.
,
Xu
Y.
,
Grinnell
B.
,
Richardson
M.
,
Topper
J.
,
Gimbrone
M.
,
Wrana
J.
,
Falb
D.
(
1997
)
The MAD-related protein Smad7 associates with the TGFreceptor and functions as an antagonist of TGF signaling.
Cell
89
,
1165
1173
Heldin
C. H.
,
Miyazano
K.
,
ten Dijke
P.
(
1997
)
TGF-signalling from cell membrane to nucleus through SMAD proteins.
Nature
390
,
465
471
Hemmati-Brivanlou
A.
,
Frank
D.
,
Bolce
M. E.
,
Brown
R. D.
,
Sive
H. L.
,
Harland
R. M.
(
1990
)
Localization of specific mRNAs in Xenopus embryos by whole-mount in situ hybridization.
Development
110
,
325
330
Hemmati-Brivanlou
A.
,
de la Torre
J.
,
Holt
C.
,
Harland
R.
(
1991
)
Cephalic expression and molecular characterization of Xenopus En-2.
Development
111
,
715
724
Hemmati-Brivanlou
A.
,
Melton
D. A.
(
1992
)
A truncated activin receptor dominantly inhibits mesoderm induction and formation of axial structures in Xenopus embryos.
Nature
359
,
609
614
Hemmati-Brivanlou
A.
,
Melton
D.
(
1994
)
Inhibition of activin receptor signaling promotes neuralization in Xenopus.
Cell
77
,
273
281
Hemmati-Brivanlou
A.
,
Kelly
O.
,
Melton
D.
(
1994
)
Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity.
Cell
77
,
283
295
Hemmati-Brivanlou
A.
,
Melton
D.
(
1997
)
Vertebrate embryonic cells will become nerve cells unless told otherwise.
Cell
88
,
13
17
Hoodless
P.
,
Haerry
T.
,
Abdollah
S.
,
Stapleton
M.
,
O'Conner
M.
,
Attisano
A.
,
Wrana
J.
(
1996
)
MADR1, a MAD-related protein that functions in BMP2 signaling pathways.
Cell
85
,
489
500
Hsu
D.
,
Economides
A.
,
Wang
X.
,
Eimon
P.
,
Harland
R. M.
(
1998
)
The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities.
Molecular Cell
1
,
673
683
Imamura
I.
,
Takase
M.
,
Nishihara
A.
,
Oeda
E.
,
Hanai
J.
,
Kawabata
M.
,
Miyazono
K.
(
1997
)
Smad6 inhibits signaling by the TGFsuperfamily.
Nature
389
,
622
626
Kintner
C.
,
Melton
D.
(
1987
)
Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction.
Development
99
,
311
325
Knecht
A.
,
Good
P.
,
Dawid
I.
,
Harland
R.
(
1995
)
Dorsal-ventral patterning and differentiation of noggin-induced neural tissue in the absence of mesoderm.
Development
121
,
1927
1936
Kretzschmar
M.
,
Liu
F.
,
Hata
A.
,
Doody
J.
,
Massague
J.
(
1997
)
The TGFfamily mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase.
Genes Dev
11
,
984
995
Krieg
P.
,
Melton
D.
(
1987
)
In vitro RNA synthesis with SP6 RNA polymerase.
Methods in Enzymology
155
,
397
415
Krieg
P. A.
,
Varnum
S.
,
Wormington
M.
,
Melton
D. A.
(
1989
)
The mRNA encoding elongation factor 1(EF-1) is a major transcript at the mid blastula transition in Xenopus.
Dev. Biol
133
,
93
100
Lagna
G.
,
Hata
A.
,
Hemmati-Brivanlou
A.
,
Massague
J.
(
1996
)
Partnership between DPC4 and SMAD proteins in TGFsignalling pathways.
Nature
383
,
832
836
Lamb
T.
,
Knecht
A.
,
Smith
W.
,
Stachel
S.
,
Economides
A.
,
Stahl
N.
,
Yancopolus
G.
,
Harland
R.
(
1993
)
Neural induction by the secreted polypeptide noggin.
Science
262
,
713
718
Lamb
T.
,
Harland
R.
(
1995
)
FGF is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern.
Development
121
,
3627
3636
Lemaire
P.
,
Gurdon
J. B.
(
1994
)
A role for cytoplasmic determinants in mesoderm patterning: cell-autonomous activation of the goosecoid and Xwnt-8 genes along the dorsoventral axis of early Xenopus embryos.
Development
120
,
1191
1199
Liu
F.
,
Hata
A.
,
Baker
J.
,
Doody
J.
,
Caracamo
J.
,
Harland
R.
,
Massague
J.
(
1996
)
A human Mad protein acting as a BMP-regulated transcriptional activator.
Nature
381
,
620
623
Liu
F.
,
Pouponnot
C.
,
Massague
J.
(
1997
)
Dual roles of Smad4/DPC4 tumor suppressor in TGF-inducible transcriptional complexes.
Genes Dev
11
,
3157
3167
Macias-Silva
M.
,
Abdollah
S.
,
Hoodless
P.
,
Pirone
R.
,
Attisano
L.
,
Wrana
J.
(
1996
)
MADR2 is a substrate of the TGFreceptor and its phosphorylation is required for nuclear accumulation and signaling.
Cell
87
,
1215
1224
Massague
J.
(
1996
)
TGFsignaling: receptors, transducers, and Mad proteins.
Cell
85
,
947
950
McGrew
L. L.
,
Lai
C. J.
,
Moon
R. T.
(
1995
)
Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signaling cascade with noggin and follistatin.
Dev. Biol
172
,
337
342
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
Nakao
A.
,
Afrakhte
M.
,
Moren
A.
,
Nakayama
T.
,
Christian
J.
,
Heuchel
R.
,
Itoh
S.
,
Kawabata
M.
,
Heldin
N.
,
Heldin
C.
,
Ten Dijke
P.
(
1997
)
Identification of Smad7, a TGF-inducible antagonist of TGF signaling.
Nature
389
,
631
635
Onichtchouk
D.
,
Gawantka
V.
,
Dosch
R.
,
Delius
H.
,
Hirschfeld
K.
,
Blumenstock
C.
,
Niehrs
C.
(
1996
)
The Xvent-2 homeobox gene is part of the BMP-4 signaling pathway controlling dorsoventral patterning of the Xenopus mesoderm.
Development
122
,
3045
3053
Piccolo
S.
,
Sasai
Y.
,
Lu
B.
,
DeRobertis
E.
(
1996
)
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
Cell
86
,
589
598
Re'em-Kalma
Y.
,
Lamb
T.
,
Frank
D.
(
1995
)
Competition between noggin and BMP4 activities may regulate dorsalization during Xenopus development.
Proc. Natl Acad. Sci. USA
92
,
12141
12145
Rebagliati
M. R.
,
Weeks
D. L.
,
Harvey
R. P.
,
Melton
D. A.
(
1985
)
Identification and cloning of localized maternal mRNAs from Xenopus eggs.
Cell
42
,
769
777
Ryan
K.
,
Garrett
N.
,
Mitchell
A.
,
Gurdon
J.
(
1996
)
Eosmesodermin, a key early gene in Xenopus mesoderm differentiation.
Cell
87
,
989
1000
Sasai
Y.
,
Lu
B.
,
Steinbeisser
H.
,
Geissert
D.
,
Gont
L.
,
De Robertis
E. M.
(
1994
)
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
Cell
79
,
779
790
Sasai
Y.
,
Lu
B.
,
Steinbeisser
H.
,
De Robertis
E. M.
(
1995
)
Regulation of neural induction by the Chd and BMP-4 antagonistic patterning signals in Xenopus.
Nature
376
,
333
336
Sasai
Y.
,
Lu
B.
,
Piccolo
S.
,
De Robertis
E.
(
1996
)
Endoderm induction by the organizer-secreted factors chordin and noggin in Xenopus animal caps.
EMBO J
15
,
4547
4555
Sasai
Y.
,
De Robertis
E.
(
1997
)
Ectodermal patterning in vertebrate embryos.
Dev. Biol
182
,
5
20
Slack
J. M. W.
(
1994
)
Inducing factors in Xenopus early embryos.
Current Biology
4
,
116
126
Smith
J. C.
(
1989
)
Mesoderm induction and mesoderm-inducing factors in early amphibian development.
Development
105
,
665
667
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) in an immediate-early response to mesoderm induction.
Cell
67
,
79
87
Smith
W. C.
,
Harland
R. M.
(
1991
)
Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
Cell
67
,
753
765
Smith
W.
,
Harland
R.
(
1992
)
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
Cell
70
,
829
840
Smith
W.
,
Knecht
A.
,
Wu
M.
,
Harland
R. M.
(
1993
)
Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm.
Nature
361
,
547
549
Smith
W. C.
,
McKendry
R. M.
,
Ribisi
S.
,
Harland
R. M.
(
1995
)
A nodal-related gene defines a physical and functional domain within the Spemann Organizer.
Cell
82
,
37
46
Wilson
P.
,
Melton
D.
(
1994
)
Mesodermal patterning by an inducer gradient depends on secondary cell-cell communication.
Current Biol
4
,
676
686
Wrana
J.
,
Attisano
L.
(
1996
)
MAD-related proteins in TGFsignaling.
Trends in Genetics
12
,
493
496
Wright
C.
,
Morita
E.
,
Wilkin
D.
,
DeRobertis
E.
(
1990
)
The Xenopus XLHbox6 homeo protein, a marker of posterior neural induction, is expressed in proliferating neurons.
Development
109
,
225
234
Yamashita
H.
,
ten Dijke
P.
,
Huylebroeck
D.
,
Sampath
T.
,
Andries
M.
,
Smith
J.
,
Heldin
C.
,
Miyazono
K.
(
1995
)
Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
J. Cell Biol
130
,
217
226
Zhang
Y.
,
Feng
X.
,
Wu
R.
,
Derynck
R.
(
1996
)
Receptor-associated Mad homologues synergize as effectors of the TGF-response.
Nature
383
,
168
172
Zimmerman
L.
,
De Jesus-Escobar
J.
,
Harland
R.
(
1996
)
The Spemann organizer signal noggin binds and inactivates BMP4.
Cell
86
,
599
606
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