Molecular mechanisms by which the mesoderm is subdivided along the mediolateral axis in early chicken embryos have been studied. When the presomitic mesoderm (medial mesoderm) was transplanted into the lateral plate, the graft was transformed into lateral plate tissue, indicating that the primitive somite was not fully committed and that the lateral plate has a cue for mesodermal lateralization. Since the lateral plate expresses a high level of BMP-4 mRNA, a member of the TGF-beta family, we hypothesized that it is the molecule responsible for the lateralization of the somite. To test this, we transplanted COS cells producing BMP-4 into the presomitic region. Those cells locally prevented the presomitic cells from differentiating into somites, converting them instead into lateral plate mesoderm, which was revealed by expression of cytokeratin mRNA, a marker for the lateral plate. The effect was dependent on the level of effective BMP-4: with a high level of BMP-4, the somite was transformed completely to lateral plate; with a low level, the somite formed but was occupied by the lateral somitic component expressing cSim 1, a marker for the lateral somite. These results suggest that different thresholds of effective BMP-4 determine distinct subtypes of the mesoderm as a lateralizer during early development.

Aoyama
H.
(
1993
)
Developmental plasticity of the prospective dermatome and the prospective sclerotome region of an avian somite.
Dev Growth Differ
35
,
507
519
Charlebois
T. S.
,
Henry
J. J.
,
Grainger
R. M.
(
1990
)
Differential cytokeratin gene expression reveals early dorsal-ventral regionalization in chick mesoderm.
Development
110
,
417
425
Charlebois
T. S.
,
Spencer
D. H.
,
Tarkington
S. K.
,
Henry
J. J.
,
Grainger
R. M.
(
1990
)
Isolation of a chicken cytokeratin cDNA clone indicative of regional specialization in early embryonic ectoderm.
Development
108
,
33
45
Christ
B.
,
Ordahl
C. P.
(
1995
)
Early stages of chick somite development.
Anat.Embryol
191
,
381
396
Deutsch
U.
,
Dressler
G. R.
,
Gruss
P.
(
1988
)
Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development.
Cell
53
,
617
625
Ebensperger
C.
,
Wilting
J.
,
Brand-Saberi
B.
,
Mizutani
Y.
,
Chrisy
B.
,
Balling
R.
,
Koseki
H.
(
1995
)
Pax-1, a regulator of sclerotome development is induced by notochord and floor plate signals in avian embryos.
Anat.Embryol
191
,
297
310
Fainsod
A.
,
Steinbeisser
H.
,
De Robertis
E. M.
(
1994
)
On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo.
EMBO J
13
,
5015
5025
Fan
C. M.
,
Tessier-Lavigne
M.
(
1994
)
Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.
Cell
79
,
1175
1186
Frasch
M.
(
1995
)
Induction of visceral and cardiac mesoderm by ectodermal dpp in the early Drosophila embryo.
Nature
374
,
464
467
Garcia-Martinez
V.
,
Schoenwolf
G. C.
(
1992
)
Positional control of mesoderm movement and fate during avian gastrulation and neurulation.
Dev. Dynamics
193
,
249
256
Goulding
M.
,
Lumsden
A.
,
Paquette
A. J.
(
1994
)
Regulation of pax-3 expression in the dermomyotome and its role in muscle development.
Development
120
,
957
971
Green
J. B. A. V. N. H.
,
Smith
J. C.
(
1992
)
Responses of embryonic Xenopus cells to Activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.
Cell
71
,
731
739
Gurdon
J. B.
,
Mitchell
A.
,
Mahony
D.
(
1995
)
Direct and continuous assessment by cells of their position in a morphogen gradient.
Nature
376
,
520
521
Hamburger
V.
,
Hamilton
H.
(
1951
)
A series of normal stages in the development of chick embryo.
J Morphol
88
,
49
92
Harland
R. M.
(
1994
)
The transforming growth factorfamily and induction of the vertebrate mesoderm: Bone morphogenetic proteins are ventral inducers.
Proc.Natl.Acad.Sci.USA
91
,
10243
10246
Johnson
R. L.
,
Laufer
E.
,
Riddle
R. D.
,
Tabin
C.
(
1994
)
Ectopic expression of sonic hedgehog alters dorsal-ventral patterning of somites.
Cell
79
,
1165
1173
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
Kimelman
D.
,
Christian
J. L.
,
Moon
R.
(
1992
)
Synergistic principles of development: overlapping patterning system in Xenopus mesoderm induction.
Development
116
,
1
9
Le Douarin
N. M.
(
1969
)
Particularites du noyau interphasique chez la Caille japonaise (Coturnix coturnix japonica). Utilisation de ces particularites comme marquage biologique dans les recherches.
Bull. Biol. Fr. Belg
103
,
435
452
Lecuit
T.
,
Brook
W. J.
,
Ng
M.
,
Calleja
M.
,
Sun
H.
,
Cohen
S. M.
(
1996
)
Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing.
Nature
381
,
387
381
Meno
C.
,
Saijoh
Y.
,
Fujii
H.
,
Ikeda
M.
,
Yokoyama
T.
,
Yokoyama
M.
,
Toyoda
Y.
,
Hamada
H.
(
1996
)
Left-right asymmetric expression of the TGF-family member lefty in mouse embryos.
Nature
381
,
151
155
Munsterberg
A. E.
,
Lassar
A. B.
(
1995
)
Combinatorial signals from the neural tube, floor plate and notochord induce myogenic bHLH gene expression in the somite.
Development
121
,
651
660
Nellen
D.
,
Burke
R.
,
Struhl
G.
,
Basler
K.
(
1996
)
Direct and long-range action of a DPP morphogen gradient.
Cell
85
,
357
368
Nishimatsu
S.-I.
,
Suzuki
A.
,
Shoda
A.
,
Murakami
K.
,
Ueno
N.
(
1992
)
Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos.
Biochem. Biophys. Res. Commun
186
,
1487
1495
Nohno
T.
,
Koyama
E.
,
Myokai
F.
,
Taniguchi
S.
,
Ohuchi
H.
,
Saito
T.
,
Noji
S.
(
1993
)
A chicken homeobox gene related to Drosophila paired is predominantly expressed in the developing limb.
Dev. Biol
158
,
254
264
Parkin
N. T.
,
Kitajewski
J.
,
Varmus
H. E.
(
1993
)
Activity of wnt-1 as a transmembrane protein.
Gene Develop
7
,
2181
2193
Parr
B. A.
,
Shea
M. J.
,
Vassileva
G.
,
McMahon
A. P.
(
1993
)
Mouse wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds.
Development
119
,
247
261
Piccolo
S.
,
Sasai
Y.
,
Lu
B.
,
DeRobertis
E. M.
(
1996
)
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
Cell
86
,
589
598
Pourquie
O.
,
Fan
C.-M.
,
Coltey
M.
,
Hirsinger
E.
,
Watanabe
Y.
,
Breant
C.
,
Francis-West
P.
,
Brickell
P.
,
Tessier-Lavigne
M.
,
Le Douarin
N. M.
(
1996
)
Lateral and axial signals involved in avian somite patterning: a role for BMP4.
Cell
84
,
461
471
Pownall
M. E.
,
Emerson
C. P.
(
1992
)
Sequential activation of three myogenic regulatory genes during somite morphogenesis in quail embryos.
Dev. Biol
151
,
67
79
Roberts
D. J.
,
Johnson
R. L.
,
Burke
A. C.
,
Nelson
C. E.
,
Morgan
B. A.
,
Tabin
C.
(
1995
)
Sonic hedgehog is an endodermal signal inducing bmp-4 and hox genes during induction and regionalization of the chick hindgut.
Development
121
,
3163
3174
Sasai
Y.
,
Lu
B.
,
Steinbeisser
H.
,
DeRobertis
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.
,
Steinbeisser
H.
,
Geissert
D.
,
Gont
L. K.
,
DeRobertis
E. M.
(
1994
)
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
Cell
79
,
779
790
Schmidt
J. E.
,
Suzuki
A.
,
Ueno
N.
,
Kimelman
D.
(
1995
)
Localized BMP-4 mediates dorsal ventral patterning in the early Xenopus embryo.
Dev. Biol
169
,
37
50
Schoenwolf
G.
,
Garcia-Martinez
V.
,
Dias
M.
(
1992
)
Mesoderm movement and fate during avian gastrulation and neurulation.
Devel. Dynam
193
,
235
248
Selleck
M.
,
Stern
C.
(
1991
)
Fate mapping and cell lineage analysis of Hensen's node in the chick embryo.
Development
112
,
615
626
Stern
C. D.
,
Fraser
S. E.
,
Keynes
R. J.
,
Primmett
D. R. N.
(
1988
)
A cell lineage analysis of segmentation in the chick embryo.
Development
104
,
231
244
Takahashi
Y.
,
Le Douarin
N. M.
(
1990
)
cDNA cloning of a quail homeobox gene and its expression in neural crest-derived mesenchyme and lateral plate mesoderm.
Proc Natl Acad Sci USA
87
,
7482
7486
Takahashi
Y.
,
Monsoro-Burq
A.-H.
,
Bontoux
M.
,
Le Douarin
N. M.
(
1992
)
A role for Quox-8 in the establishment of the dorsoventral pattern during vertebrate development.
Proc Nat Acad Sci USA
89
,
10237
10241
van Straaten
H. W. M.
,
Hekking
J. W. M.
(
1991
)
Development of floor plate, neurons and axonal outgrowth pattern in the early spinal cord of the notochord-deficient chick embryo.
Anat. Embryol
184
,
55
63
Watanabe
Y.
,
LeDouarin
N. M.
(
1996
)
A role for BMP-4 in the development of subcutaneous cartilage.
Mech. Dev
57
,
69
78
Weintraub
H.
,
Davis
R.
,
Tapscott
S.
,
Thayer
M.
,
Krause
M.
,
Benezra
R.
,
Blackwell
T. K.
,
Turner
D.
,
Rupp
R.
,
Hollenberg
S.
,
Zhuang
Y.
(
1991
)
The myoD gene family: Nodal point during specification of the muscle cell lineage.
Science
251
,
761
766
Williams
B. A.
,
Ordahl
C. P.
(
1994
)
Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification.
Development
120
,
785
796
Wilson
P. A.
,
Hemmati-Brivanlou
A.
(
1995
)
Induction of epidermis and inhibition of neural fate by bmp-4.
Nature
376
,
331
333
Winnier
G.
,
Blessing
M.
,
Labosky
P. A.
,
Hogan
B. L. M.
(
1995
)
Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.
Gene Develop
9
,
2105
2116
Zimmerman
L. B.
,
DeJesus-Escobar
J. M.
,
Harland
R. M.
(
1996
)
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
Cell
86
,
599
606
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