One of the first intercellular signalling events in the vertebrate embryo leads to mesoderm formation and axis determination. In the mouse, a gene encoding a new member of the TGF-beta superfamily, nodal, is disrupted in a mutant deficient in mesoderm formation (Zhou et al., 1993, Nature 361, 543). nodal mRNA is found in prestreak mouse embryos, consistent with a role in the development of the dorsal axis. To examine the biological activities of nodal, we have studied the action of this factor in eliciting axis determination in the zebrafish, Danio rerio. Injection of nodal mRNA into zebrafish embryos caused the formation of ectopic axes that included notochord and somites. Axis duplication was preceded by the generation of an apparent ectopic shield (organizer equivalent) in nodal-injected embryos, as indicated by the appearance of a region over-expressing gsc and lim1; isolation and expression in the shield of the lim1 gene is reported here. These results suggest a role for a nodal-like factor in pattern formation in zebrafish.

Reference

Abdeillah
S.
,
Solnica-Krezel
L.
,
Stainier
D.Y.R.
,
Driever
W.
(
1994
)
Implications for dorsoventral axis determination from the zebrafish mutation janus.
Nature
370
,
468
471
Barnes
J.D.
,
Crosby
J.L.
,
Jones
C.M.
,
Wright
C.V.E.
,
Hogan
B.L.M.
(
1994
)
Embryonic expression of Lim-1, the mouse homolog of Xenopu s XLim-1, suggests a role in lateral mesoderm differentiation and neurogenesis.
Dev. Biol
161
,
168
178
Beddington
R.S.P.
(
1994
)
Induction of a second neural axis by the mouse node.
Development
120
,
613
620
Blum
M.
,
Gaunt
S.J.
,
Cho
K.W.Y.
,
Steinbeisser
H.
,
Blumberg
B.
,
Bittner
D.
,
De Robertis
E.M.
(
1992
)
Gastrulation in the mouse: the role of the homeobox gene goosecoid.
Cell
69
,
1097
1106
Bolce
M.E.
,
Hemmati-Brivanlou
A.
,
Kushner
P.D.
,
Harland
R.M.
(
1992
)
Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin.
Development
115
,
681
688
Cho
K.W.Y.
,
Blumberg
B.
,
Steinbeisser
H.
,
De Robertis
E.M.
(
1991
)
Molecular nature of Spemann's Organizer: the role of the Xenopus homeobox gene goosecoid.
Cell
67
,
1111
1120
Chomczynski
P.
,
Sacchi
N.
(
1987
)
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal. Biochem
162
,
156
159
Conlon
F.L.
,
Lyons
K.M.
,
Takaesu
N.
,
Barth
K.S.
,
Kispert
A.
,
Herrmann
B.
,
Robertson
E.J.
(
1994
)
A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse.
Development
120
,
1919
1938
Dale
L.
,
Howes
G.
,
Price
B.M.J.
,
Smith
J.C.
(
1992
)
Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development.
Development
115
,
573
585
Dale
L.
,
Matthews
G.
,
Colman
A.
(
1993
)
Secretion and mesoderm-inducing activity of the TGF--related domain of Xenopus Vg1.
EMBO J
12
,
4471
4480
Dawid
I.B.
(
1994
)
Intercellular signaling and gene regulation during early embryogenesis of Xenopus laevis.
J. Biol. Chem
269
,
6259
6262
Fujii
T.
,
Pichel
J.G.
,
Taira
M.
,
Toyama
R.
,
Dawid
I. B.
,
Westphal
H.
(
1994
)
Expression patterns of the murine LIM class homeobox gene lim1 in the developing brain and excretory system.
Dev. Dynamics
199
,
73
83
Gerhart
J.
,
Danilchik
M.
,
Doniach
T.
,
Roberts
S.
,
Rowning
B.
,
Stewart
R.
(
1989
)
Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development.
Development
107
,
37
51
Gilbert
S.F.
,
Saxen
L.
(
1993
)
Spemann's Organizer: models and molecules.
Mech. Dev
41
,
73
89
Hemmati-Brivanlou
A.
,
Harland
R.M.
(
1989
)
Expression of an engrailed -related protein is induced in the anterior neural ectoderm of early Xenopus embryos.
Development
106
,
611
617
Helde
K.A.
,
Wilson
E.T.
,
Cretekos
C.J.
,
Grunwald
D.J.
(
1994
)
Contribution of early cells to the fate map of the zebrafish gastrula.
Science
265
,
517
520
Jones
C.M.
,
Lyons
K.M.
,
Lapan
P.M.
,
Wright
C.V.E.
,
Hogan
B.L.M.
(
1992
)
DVR-4 (Bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.
Development
115
,
639
647
Kimmel
C.B.
,
Warga
R.M.
,
Schilling
T.F.
(
1990
)
Origin and organization of the zebrafish fate map.
Development
108
,
581
594
Kimelman
D.
,
Kirschner
M.
(
1987
)
Synergistic induction of mesoderm by FGF and TGF-and the identification of an mRNA coding for FGF in the early Xenopus embryo.
Cell
51
,
869
877
Kimelman
D.
,
Christian
J.L.
,
Moon
R.T.
(
1992
)
Synergistic principles of development: overlapping patterning systems in Xenopus mesoderm induction.
Development
116
,
1
9
Kintner
C.R.
,
Dodd
J.
(
1991
)
Henson's node induces neural tissue in Xenopus ectoderm. Implications for the action of the organizer in neural induction.
Development
113
,
1495
1505
Krieg
P.A.
,
Melton
D.A.
(
1984
)
Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs.
Nucleic Acids Res
12
,
7057
7070
Moon
R.T.
(
1993
)
In pursuit of the functions of the Wnt family of developmental regulators: Insights from Xenopus laevis.
Bioessays
15
,
91
97
Schulte-Merker
S.
,
Ho
R.K.
,
Herrmann
B.G.
,
Nusslein-Volhard
C.
(
1992
)
The protein product of the zebrafish homologue of the mouse T gene is expressed in nuclei of the germ ring and the notochord of the early embryo.
Development
116
,
1021
1032
Schulte-Merker
S.
,
Hammerschmidt
M.
,
Beuchle
D.
,
Cho
K.W.
,
De Robertis
E.M.
,
Nusslein-Volhard
C.
(
1994
)
Expression of zebrafish goosecoid and no tail gene products in wild-type and mutant no tail embryos.
Development
120
,
843
852
Schulte-Merker
S.
,
van Eeden
F.J.M.
,
Halpern
M.E.
,
Kimmel
C.B.
,
Nusslein-Volhard
C.
(
1994
)
no tail (ntl) is the zebrafish homolog of the mouse T (Brachyury) gene.
Development
120
,
1009
1015
Schulte-Merker
S.
,
Smith
J.C.
,
Dale
L.
(
1994
)
Effects of truncated activin and FGF receptors and follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction?.
EMBO J
13
,
3533
3541
Slack
J.M.W.
,
Darlington
B.G.
,
Heath
J.K.
,
Godsave
S.F.
(
1987
)
Mesoderm induction in early Xenopus embryos by heparin-binding growth factors.
Nature
326
,
197
200
Slack
J.
(
1993
)
Embryonic Induction.
Mechanisms of Devel
41
,
91
107
Smith
J. C.
,
Price
B.M.J.
,
Van Nimmen
K.
,
Huylebroeck
D.
(
1990
)
Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A.
Nature
345
,
729
731
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.C.
,
Harland
R.M.
(
1992
)
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
Cell
70
,
829
840
Sokol
S.
,
Christian
J.L.
,
Moon
R.T.
,
Melton
D.A.
(
1991
)
Injected Wnt RNA induces a complete body axis in Xenopus embryos.
Cell
67
,
741
752
Stachel
S.E.
,
Grunwald
D.J.
,
Myers
P.Z.
(
1993
)
Lithium perturbation and goosecoid expression identify a dorsal specification pathway in the pregastrula zebrafish.
Development
117
,
1261
1274
Steinbeisser
H.
,
DeRobertis
E.M.
(
1993
)
Xenopus goosecoid: A gene expressed in the prechordal plate that has dorsalizing activity.
Comptes Rendus Acad. Sci
316
,
966
971
Strähle
U.
,
Blader
P.
,
Henrique
D.
,
Ingham
P.W.
(
1993
)
Axial, a zebrafish gene expressed along the developing body axis, shows altered expression in cyclops mutant embryos.
Genes Dev
7
,
1436
1446
Strehlow
D.
,
Gilbert
W.
(
1993
)
A fate map for the first cleavages of the zebrafish.
Nature
361
,
451
453
Strehlow
D.
,
Heinrich
G.
,
Gilbert
W.
(
1994
)
The fates of the blastomeres of the 16-cell zebrafish embryo.
Development
120
,
1791
1798
Taira
M.
,
Jamrich
M.
,
Good
P.J.
,
Dawid
I.B.
(
1992
)
The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.
Gene Dev
6
,
356
366
Taira
M.
,
Otani
H.
,
Jamrich
M.
,
Dawid
I.B.
(
1994
)
Expression of the LIM class homeobox gene Xlim-1 in pronephros and CNS cell lineages of Xenopus embryos is affected by retinoic acid and exogastrulation.
Development
120
,
1525
1536
Thisse
C.
,
Thisse
B.
,
Halpern
M.E.
,
Postlethwait
J.H.
(
1994
)
goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas.
Dev. Biol
164
,
420
429
Thomsen
G.
,
Woolf
T.
,
Whitman
M.
,
Sokol
S.
,
Vaughan
J.
,
Vale
W.
,
Melton
D.A.
(
1990
)
Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures.
Cell
63
,
485
493
Thomsen
G.H.
,
Melton
D.A.
(
1993
)
Processed Vg1 protein is an axial mesoderm inducer in Xenopus.
Cell
74
,
433
441
Vize
P.D.
,
Melton
D.A.
,
Hemmati-Brivanlou
A.
,
Harland
R.M.
(
1991
)
Assays for gene function in developing Xenopus embryos.
Meth. Cell Biol
36
,
367
387
Warga
R.M.
,
Kimmel
C.B.
(
1990
)
Cell movements during epiboly and gastrulation in zebrafish.
Development
108
,
569
580
Wilson
E.T.
,
Helde
K.A.
,
Grunwald
D.J.
(
1993
)
Something's fishy here-rethinking cell movements and cell fate in the zebrafish embryo.
Trends Genet
9
,
10
–.
Wittbrodt
J.
,
Rosa
F.M.
(
1994
)
Disruption of mesoderm and axis formation in fish by ectopic expression of activin variants: the role of maternal activin.
Genes Dev
8
,
1448
1462
Zhou
X.
,
Sasaki
H.
,
Lowe
L.
,
Hogan
B.L.M.
,
Kuehn
M.R.
(
1993
)
Nodal is a novel TGF--like gene expressed in the mouse node during gastrulation.
Nature
361
,
543
547
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