Embryonic muscle growth requires a fine balance between proliferation and differentiation. In this study we have investigated how this balance is achieved during chick development. Removal of ectoderm from trunk somites results in the down-regulation of Pax-3 expression and cell division of myogenic precursors is halted. This initially leads to an up-regulation of MyoD expression and to a burst in terminal differentiation but further muscle growth is arrested. Locally applied bone morphogenetic protein-4 (BMP-4) to somites mimics the effect of the ectoderm and stimulates Pax-3 expression which eventually results in excessive muscle growth in somites. Surprisingly, BMP-4 up-regulates expression of noggin which encodes a BMP-4 antagonist. This suggests that the proliferation enhancing activity of BMP-4 can be limited via up-regulation of noggin and that myogenic cells differentiate, as an intrinsic property, when deprived of BMP-4 influence. In contrast to BMP-4, Sonic hedgehog (Shh) locally applied to somites arrests muscle growth by down-regulation of Pax-3 and immediate up-regulation of MyoD expression. Such premature muscle differentiation in somites at tongue and limb levels prevents myogenic migration and thus tongue and limb muscle are not formed. Therefore, precise limitation of differentiation, executed by proliferative and Pax-3 promoting signals, is indispensable for continuous embryonic muscle growth.
Reference
Amthor
H.
, Connolly
D.
, Patel
K.
, Brand-Saberi
B.
, Wilkinson
D. G.
, Cooke
J.
, Christ
B.
(1996
) The expression and regulation of follistatin and a follistatin-like gene during avian somite compartmentalization and myogenesis.
Dev. Biol
178
, 343
–362
Amthor
H.
, Christ
B.
, Weil
M.
, Patel
K.
(1998
) The importance of timing differentiation during limb muscle development.
Curr. Biol
8
, 642
–652
Bladt
F.
, Riethmacher
D.
, Isenmann
S.
, Aguzzi
A.
, Birchmeier
C.
(1995
) Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud.
Nature
376
, 768
–771
Borycki
A. G.
, Mendham
L.
, Emerson
C. P.
Jr (1998
) Control of somite patterning by Sonic hedgehog and its down stream signal response genes.
Development
125
, 770
–790
Brand-Saberi
B.
, Muller
T. S.
, Wilting
J.
, Christ
B.
, Birchmeier
C.
(1996
) Scatter Factor/Hepatocyte Growth Factor (SF/HGF) induces emigration of myogenic cells at interlimb level in vivo.
Dev. Biol
179
, 303
–308
Christ
B.
, Jacob
H. J.
, Jacob
M.
(1977
) Experimental analysis of the origin of the wing musculature in avian embryos.
Anat. Embryol
150
, 171
–186
Christ
B.
, Jacob
M.
, Jacob
H. J.
(1983
) On the origin and development of the ventroabdominal muscles in the avian embryo.
Anat. Embryol
166
, 87
–101
Christ
B.
, Ordahl
C. P.
(1995
) Early stages of chick somite development.
Anat. Embryol
191
, 381
–396
Cohn
M. J.
, Izpisua-Belmonte
J. C.
, Abud
H.
, Heath
J. K.
, Tickle
C.
(1995
) Fibroblast growth factors induce additional limb development from the flank of chick embryos.
Cell
80
, 739
–746
Cossu
G.
, Tajbakhsh
S.
, Buckingham
M.
(1996
) How is myogenesis initiated in the embryo?.
Trends Genet
12
, 218
–223
Cossu
G.
, Kelly
R.
, Tajbakhsh
S.
, Di Donna
S.
, Vivarelli
E.
, Buckingham
M.
(1996
) Activation of different myogenic pathways: myf-5 is induced by the neural tube and MyoD by the dorsal ectoderm in mouse paraxial mesoderm.
Development
122
, 429
–437
Currie
P. D.
, Ingham
P. W.
(1996
) Induction of a specific muscle cell type by a hedgehog-like protein in zebrafish.
Nature
382
, 452
–455
Dahl
E.
, Koseki
H.
, Balling
R.
(1997
) Pax genes and organogenesis.
BioEssays
19
, 755
–765
Denetclaw
W. F.
Jr., Christ
B.
, Ordahl
C. P.
(1997
) Location andgrowth of epaxial myotome precursor cells.
Development
124
, 1601
–1610
Detwiler
S. R.
(1926
) The effect of reduction of skin and of muscle on the development of spinal ganglia.
J. Exp. Zool
45
, 399
–414
Dietrich
S.
, Schubert
F. R.
, Lumsden
A.
(1997
) Control of dorsoventral pattern in the chick paraxial mesoderm.
Development
124
, 3895
–3908
Dietrich
S.
, Schubert
F. R.
, Healy
C.
, Sharpe
P. T.
, Lumsden
A.
(1998
) Specification of the hypaxial musculature.
Development
125
, 2235
–2249
Duprez
D.
, Fournier-Thibault
C.
, Le Douarin
N.
(1998
) Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb.
Development
125
, 495
–505
Duxson
M. F.
, Sheard
P. W.
(1995
) Formation of new myotubes occurs exclusively at the multiple innervation zones of an embryonic large muscle.
Dev. Dyn
204
, 391
–405
Epstein
J. A.
, Shapiro
D. N.
, Cheng
J.
, Lam
P. Y. P.
, Maas
R. L.
(1996
) Pax3 modulates expression of the c-Met receptor during limb muscle development.
Proc. Natl. Acad. Sci. USA
93
, 4213
–4218
Fan
C.-M.
, Lee
C. S.
, Tessier-Lavigne
M.
(1997
) A role for WNTproteins in induction of dermomyotome.
Dev. Biol
191
, 160
–165
Franz
T.
, Kothary
R.
, Surani
M. A.
, Halata
Z.
, Grim
M.
(1993
) The Splotch mutation interferes with muscle development in the limbs.
Anat. Embryol
187
, 153
–160
Fredericks
W. J.
, Galili
N.
, Mukhopadhyay
S.
, Rovera
G.
, Bennicelli.
J.
, Barr
F. G.
, Rauscher
F. J.
3rd (1995
) The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.
Mol. Cell Biol
15
, 1522
–1535
George-Weinstein
M.
, Gerhart
J.
, Reed
R.
, Flynn
J.
, Callihan
B.
, Mattiacci
M.
, Miehle
C.
, Foti
G.
, Lash
J. W.
, Weintraub
H.
(1996
) Skeletal myogenesis: The preferred pathway of chick embryo epiblast cells in vitro.
Dev. Biol
173
, 279
–291
Hamburger
V.
, Hamilton
H. L.
(1951
) A series of normal stages in the development of the chick embryo.
J. Morphol
88
, 49
–92
Hirsinger
E.
, Duprez
D.
, Fouve
C.
, Malapert
P.
, Cooke
J.
, Pourquie
O.
(1997
) Noggin acts downstream of Wnt and Sonic hedgehog to antagonize BMP4 in avian somite patterning.
Development
124
, 4605
–4614
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
Kaehn
K.
, Jacob
H. J.
, Christ
B.
, Hinrichsen
K.
, Poelmann
R. E.
(1988
) The onset of myotome formation in the chick.
Anat. Embryol
177
, 191
–201
Kahane
N.
, Cinnamon
Y.
, Kalcheim
C.
(1998
) The origin and fate of pioneer myotomal cells in the avian embryo.
Mech. Dev
74
, 59
–73
Kahane
N.
, Cinnamon
Y.
, Kalcheim
C.
(1998
) The cellular mechanism by which the dermomyotome contributes to the second wave of myotome development.
Development
125
, 4259
–4271
Marcelle
C.
, Stark
M. R.
, Bronner-Fraser
M.
(1997
) Coordinate action of BMPs, Wnts, Shh and Noggin mediate patterning of the dorsal somite.
Development
124
, 3955
–3963
Marigo
V.
, Davey
R. A.
, Zuo
Y.
, Cunningham
J. M.
, Tabin
C. J.
(1996
) Biochemical evidence that Patched is the Hedgehog receptor.
Nature
384
, 176
–179
Marigo
V.
, Scott
M. P.
, Johnson
R. L.
, Goodrich
L. V.
, Tabin
C. J.
(1996
) Conservation in hedgehog signaling: induction of a chicken patched homolog by Sonic hedgehog in the developing limb.
Development
122
, 1225
–1233
Maroto
M.
, Reshef
R.
, Munsterberg
A. E.
, Koester
S.
, Goulding
M.
, Lassar
A. B.
(1997
) Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue.
Cell
89
, 139
–148
Marti
E.
, Takada
R.
, Bumcrot
D. A.
, Sasaki
H.
, McMahon
A. P.
(1995
) Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo.
Development
121
, 2537
–2547
Monsoro-Burq
A. H.
, Duprez
D.
, Watanabe
Y.
, Bontoux
M.
, Vincent
C.
, Brickell
P.
, Le Douarin
N.
(1996
) The role of bone morphogenetic proteins in vertebral development.
Development
122
, 3607
–3616
Munsterberg
A. E.
, Kitajewski
J.
, Bumcrot
D. A.
, McMahon
A. P.
, Lassar
A. B.
(1995
) Combinatorial signaling by Sonic hedgehog and Wnt family members induces myogenic bHLH gene expression in the somite.
Genes Dev
9
, 2911
–2922
Nieto
M. A.
, Patel
K.
, Wilkinson
D. G.
(1996
) In situ hybridization analysis of chick embryos in whole mount and tissue sections.
Methods Cell Biol
51
, 219
–235
Olson
E. N.
(1992
) Interplay between proliferation and differentiation within the myogenic lineage.
Dev. Biol
154
, 261
–272
Ordahl
C. P.
, Le Douarin
N. M.
(1992
) Two myogenic lineages within the developing somite.
Development
114
, 339
–353
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
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.
Jr (1992
) Sequential activation of three myogenic regulatory genes during somite morphogenesis in quail embryos.
Dev. Biol
151
, 67
–79
Schemainda
H.
(1979
) Über die Entwicklung der occipitalen Somiten. Experimentelle Untersuchungen an Wachtel-und Huhnerembryonen.
Verh. Anat. Ges
73
, 527
–532
Sechrist
J.
, Marcelle
C.
(1996
) Cell division and differentiation an avian embryos: techniques for study of early neurogenesis and myogenesis.
Methods Cell Biol
51
, 301
–329
Shapiro
D. N.
, Sublett
J. E.
, Li
B.
, Downing
J. R.
, Naeve
C. W.
(1993
) Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma.
Cancer Res
53
, 5108
–5112
Spence
M. S.
, Yip
J.
, Erickson
C. A.
(1996
) The dorsal neural tube organizes the dermamyotome and induces axial myocytes in the avian embryo.
Development
122
, 231
–241
Stern
H. M.
, Brown
A. M.
, Hauschka
S. D.
(1995
) Myogenesis inparaxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1.
Development
121
, 3675
–3686
Strachan
T.
, Read
A. P.
(1994
) PAX genes.
Curr. Opin. Genet. Dev
4
, 427
–438
Tajbakhsh
S.
, Rocancourt
D.
, Buckingham
M.
(1996
) Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice.
Nature
384
, 266
–270
Tajbakhsh
S.
, Rocancourt
D.
, Cossu
G.
, Buckingham
M.
(1997
) Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD.
Cell
89
, 127
–138
Tajbakhsh
S.
, Borello
U.
, Vivarelli
E.
, Kelly
R.
, Papkoff
J.
, Duprez
D.
, Buckingham
M.
, Cossu
G.
(1998
) Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.
Development
125
, 4155
–4162
Teillet
M.-A.
, Watanabe
Y.
, Jeffs
P.
, Duprez
D.
, Lapointe
F.
, Le Douarin
N. M.
(1998
) Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages.
Development
125
, 2019
–2030
Tonegawa
A.
, Funayama
N.
, Ueno
N.
, Takahashi
Y.
(1997
) Mesodermal subdivisions along the mediolateral axis in chicken controlled by different concentrations of BMP-4.
Development
124
, 1975
–1984
Weintraub
H.
, Davis
R.
, Tapscott
S.
, Thayer.
M.
, Krause
M.
, Benezra
R.
, Blackwell
T. K.
, Turner
D.
, Rupp
R.
, Hollenberg
S.
, et al. (1991
) The myoD gene family: nodal point during specification of the muscle cell lineage.
Science
251
, 761
–766
Weil
M.
, Jacobson
M. D.
, Raff
M. C.
(1997
) Is programmed cell death required for neural tube closure?.
Curr. Biol
7
, 281
–284
Williams
B. A.
, Ordahl
C. P.
(1994
) Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification.
Development
120
, 785
–796
Williams
B. A.
, Ordahl
C. P.
(1997
) Emergence of determined myotome precursor cells in the somite.
Development
124
, 4983
–4997
Zimmerman
L. B.
, De Jesus-Escobar
J. M.
, Harland
R. M.
(1996
) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
Cell
86
, 599
–606
This content is only available via PDF.
© 1999 by Company of Biologists
1999
