Specification of the myogenic lineage begins prior to gastrulation and culminates in the emergence of determined myogenic precursor cells from the somites. The myoD family (MDF) of transcriptional activators controls late step(s) in myogenic specification that are closely followed by terminal muscle differentiation. Genes expressed in myogenic specification at stages earlier than MDFs are unknown. The Pax-3 gene is expressed in all the cells of the caudal segmental plate, the early mesoderm compartment that contains the precursors of skeletal muscle. As somites form from the segmental plate and mature, Pax-3 expression is progressively modulated. Beginning at the time of segmentation, Pax-3 becomes repressed in the ventral half of the somite, leaving Pax-3 expression only in the dermomyotome. Subsequently, differential modulation of Pax-3 expression levels delineates the medial and lateral halves of the dermomyotome, which contain precursors of axial (back) muscle and limb muscle, respectively. Pax-3 expression is then repressed as dermomyotome-derived cells activate MDFs. Quail-chick chimera and ablation experiments confirmed that the migratory precursors of limb muscle continue to express Pax-3 during migration. Since limb muscle precursors do not activate MDFs until 2 days after they leave the somite, Pax-3 represents the first molecular marker for this migratory cell population. A null mutation of the mouse Pax-3 gene, Splotch, produces major disruptions in early limb muscle development (Franz, T., Kothary, R., Surani, M. A. H., Halata, Z. and Grim, M. (1993) Anat. Embryol. 187, 153–160; Goulding, M., Lumsden, A. and Paquette, A. (1994) Development 120, 957–971). We conclude, therefore, that Pax-3 gene expression in the paraxial mesoderm marks earlier stages in myogenic specification than MDFs and plays a crucial role in the specification and/or migration of limb myogenic precursors.

REFERENCES

REFERENCES
Beddington
R. S. P.
,
Martin
P.
(
1989
)
An in situ transgenic enzyme marker to monitor migration of cells in the mid-gestation mouse embryo: somite contribution to the forelimb.
Mol. Biol. Med
6
,
263
274
Beresford
B.
(
1983
)
Brachial muscles in the chick embryo: the fate of individual somites.
J. Embryol. exp. Morph
77
,
99
116
Bonner
P. H.
,
Hauschka
S. D.
(
1974
)
Clonal analysis of vertebrate myogenesis: Early developmental events in the chick limb.
Dev. Biol
37
,
317
328
Braun
T.
,
Rudnicki
M.
,
Arnold
H.
,
Jaenisch
R.
(
1992
)
Targeted inactivation of the muscle regulatory gene myf-5 results in abnormal rib development and perinatal death.
Cell
71
,
369
382
Charles de la Brousse
F.
,
Emerson
C. P.
(
1990
)
Localized expression of a myogenic regulatory gene, qmf1, in the somite dermatome of avian embryos.
Genes Dev
4
,
567
581
Chevallier
A.
,
Kieny
M.
,
Mauger
A.
(
1977
)
Limb-somite relationship: Origin of the limb musculature.
J. Embryol. exp. Morph
41
,
245
258
Chevallier
A.
,
Kieny
M.
,
Mauger
A.
(
1978
)
Limb-somite relationship: effect of removal of somitic mesoderm on the wing musculature.
J. Embryol. exp. Morph
43
,
263
278
Chiquet-Ehrismann
R.
(
1991
)
Anti-adhesive molecules of the extracellular matrix.
Curr. Op. Cell Biol
3
,
800
804
Choi
J.
,
Costa
M. L.
,
Mermelstein
C. S.
,
Chagas
C.
,
Holtzer
S.
,
Holtzer
H.
(
1990
)
MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblasts and multinucleated myotubes.
Proc. Natl. Acad. Sci. USA
87
,
7988
7992
Christ
B.
,
Jacob
H.
,
Jacob
M.
(
1974
)
Uber den ursprung der flugelmuskulature.
Experientia
30
,
1446
1448
Christ
B.
,
Jacob
H.
,
Jacob
M.
(
1977
)
Experimental analysis of the origin of the wing musculature in avian embryos.
Anat. Embryol
150
,
171
186
Corbin
V.
,
Michelson
A. M.
,
Abmayr
S. M.
,
Neel
V.
,
Alcamo
E.
,
Maniatis
T.
,
Young
M. W.
(
1991
)
A role for the Drosophila neurogenic genes in mesoderm differentiation.
Cell
67
,
311
323
Cserjesi
P.
,
Lilly
B.
,
Bryson
L.
,
Wang
Y.
,
Sassoon
D. A.
,
Olson
E. N.
(
1992
)
MHox: a mesodermally restricted homeodomain protein that binds an essential site in the muscle creatine kinase enhancer.
Development
115
,
1087
1101
Dienstman
S. R.
,
Biehl
J.
,
Holtzer
S.
,
Holtzer
H.
(
1974
)
Myogenic and chondrogenic lineages in developing limb buds grown in vitro.
Dev. Biol
39
,
83
95
Emerson
C. P.
(
1993
)
Skeletal myogenesis: genetics and embryology to the fore.
Curr. Op. Gen. Dev
3
,
265
274
Epstein
D.
,
Vekemans
M.
,
Gros
P.
(
1991
)
Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3.
Cell
67
,
767
774
Franz
T.
(
1993
)
The Splotch (Sp1H) and Splotch-delayed (Spd) alleles: differential phenotypic effects on neural crest and limb musculature.
Anat. Embryol
187
,
371
377
Franz
T.
,
Kothary
R.
,
Surani
M. A. H.
,
Halata
Z.
,
Grim
M.
(
1993
)
The Splotch mutation interferes with muscle development in the limbs.
Anat. Embryol
187
,
153
160
Frohman
M. A.
,
Boyle
M.
,
Martin
G. R.
(
1990
).
Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm.
Development
110
,
589
607
Goulding
M.
,
Sterrer
S.
,
Fleming
J.
,
Balling
R.
,
Nadeau
J.
,
Moore
K.
,
Brown
S.
,
Steel
K.
,
Gruss
P.
(
1993
)
Analysis of the Pax-3 gene in the mouse mutant Splotch.
Genomics
17
,
355
363
Goulding
M. D.
,
Chalepakis
G.
,
Deutsch
U.
,
Erselius
J. R.
,
Gruss
P.
(
1991
)
Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.
EMBO J
10
,
1135
1147
Goulding
M. D.
,
Lumsden
A.
,
Gruss
P.
(
1993
)
Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord.
Development
117
,
1001
1016
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
Gruss
P.
,
Walther
C.
(
1992
)
Pax in development.
Cell
69
,
719
722
Halpern
M. E.
,
Ho
R. K.
,
Walker
C.
,
Kimmel
C. B.
(
1993
)
Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation.
Cell
75
,
99
111
Hamburger
V.
,
Hamilton
H. L.
(
1951
)
A series of normal stages in the development of the chick embryo.
J. Morphol
88
,
49
92
Hamburger
V.
,
Hamilton
H. L.
(
1992
)
A series of normal stages in the development of the chick embryo.
Dev. Dynam
195
,
231
272
Hartenstein
A. Y.
,
Rugendorff
A.
,
Tepass
U.
,
Hartenstein
V.
(
1992
)
The function of the neurogenic genes during epithelial development in the Drosophila embryo.
Development
116
,
1203
1220
Hasty
P.
,
Bradley
A.
,
Morris
J.
,
Edmondson
D.
,
Venuti
J.
,
Olson
E.
,
Klein
W.
(
1993
)
Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene.
Nature
364
,
501
506
Heitzler
P.
,
Simpson
P.
(
1991
)
The choice of cell fate in the epidermis of Drosophila.
Cell
64
,
1083
1092
Jones
F. S.
,
Prediger
E. A.
,
Bittner
D. A.
,
DeRobertis
E. M.
,
Edelman
G. M.
(
1992
).
Cell adhesion molecules as targets for Hox genes: Neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4.
Proc. Natl. Acad. Sci. USA
89
,
2086
2090
Kaehn
K.
,
Jacob
H. J.
,
Christ
B.
,
Hinrichsen
K.
,
Poelmann
R.
(
1988
)
The onset of myotome formation in the chick.
Anat. Embryol
177
,
191
201
Keynes
R.
,
Stern
C.
(
1988
)
Mechanisms of vertebrate segmentation.
Development
103
,
413
429
Krenn
V.
,
Gorka
P.
,
Wachtler
F.
,
Christ
B.
,
Jacob
H. J.
(
1988
)
On the origin of cells determined to form skeletal muscle in avian embryos.
Anat. Embryol
179
,
49
54
Le Douarin
N. M.
(
1973
)
A Feulgen-positive nucleus.
Exp. Cell Res
77
,
459
468
Lin
Z.
,
Dechesne
C. A.
,
Eldridge
J.
,
Paterson
B. M.
(
1989
)
An avian muscle factor related to MyoD1 activates muscle-specific promoters in nonmuscle cells of different germ-layer origin and in BrdU-treated myoblasts.
Genes Dev
3
,
986
996
Moase
C. E.
,
Trasler
D. G.
(
1990
)
Delayed neural crest cell emigration from Sp and Spdmouse neural tube explants.
Teratology
42
,
171
182
Moase
C. E.
,
Trasler
D. G.
(
1991
)
N-CAM alteration in splotch neural tube defect mouse embryos.
Development
113
,
1049
1058
Nabeshima
Y.
,
Hanaoka
K.
,
Hayasaka
M.
,
Esumi
E.
,
Li
S.
,
Nonaka
I.
,
Nabeshima
Y.
(
1993
)
Myogenin gene disruption results in perinatal lethality because of severe muscle defect.
Nature
364
,
532
535
Newman
S. A.
,
Pautou
M.-P.
,
Kieny
M.
(
1981
)
The distal boundary of myogenic primordia in chimeric avian limb buds and its relation to an accessible population of cartilage progenitor cells.
Dev. Biol
84
,
440
448
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
Ott
M.
,
Bober
E.
,
Lyons
G.
,
Arnold
H.
,
Buckingham
M.
(
1991
)
Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo.
Development
111
,
1097
1107
Pourquie
O.
,
Coultey
M.
,
Teillet
M.-A.
,
Ordahl
C. P.
,
Le Douarin
N. M.
(
1993
)
Control of dorsoventral patterning of the somitic derivatives by notochord and floor plate.
Proc. Natl. Acad. Sci. USA
90
,
5242
5246
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
Reaume
A. G.
,
Conlon
R. A.
,
Zirngibl
R.
,
Yamaguchi
T. P.
,
Rossant
J.
(
1992
)
Expression analysis of a Notch homologue in the mouse embryo.
Dev. Biol
154
,
377
387
Rong
P. M.
,
Teillet
M.-A.
,
Ziller
C.
,
Le Douarin
N. M.
(
1992
)
The neural tube/notochord complex is necessary for vertebral but not limb and body wall striated muscle differentiation.
Development
115
,
657
672
Rudnicki
M.
,
Braun
T.
,
Hinuma
S.
,
Jaenisch
R.
(
1992
)
Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development.
Cell
71
,
383
390
Rutz
R.
,
Haney
C.
,
Hauschka
S.
(
1982
)
Spatial analysis of limb bud myogenesis: A proximodistal gradient of muscle colony-forming cells in chick embryo leg buds.
Dev. Biol
90
,
399
411
Searls
R.
,
Janners
M.
(
1969
)
The stabilization of cartilage properties in the cartilage-forming mesenchyme of the embryonic chick limb.
J. Exp. Zool
170
,
365
376
Seed
J.
,
Hauschka
S. D.
(
1984
)
Temporal separation of the migration of distinct myogenic precursor populations into the developing chick wing bud.
Dev. Biol
106
,
389
393
Selleck
M.
,
Stern
C.
(
1991
)
Fate mapping and cell lineage analysis of Hensen's node in the chick embryo.
Development
112
,
615
626
Stark
R.
,
Searls
R.
(
1974
)
The establishment of the cartilage pattern in the embryonic chick wing, and evidence for a role of the dorsal and ventral ectoderm in normal wing development.
Dev. Biol
38
,
51
63
Tan
S.-S.
,
Prieto
A. L.
,
Newgreen
D. F.
,
Crossin
K. L.
,
Edelman
G. M.
(
1991
)
Cytotactin expression in somites after dorsal neural tube and neural crest ablation in chicken embryos.
Proc. Natl. Acad. Sci. USA
88
,
6398
6402
Weintraub
H.
,
Davis
R.
,
Tapscott
S.
,
Thayer
M.
,
Krause
M.
,
Benezra
R.
,
Blackwell
T. K.
,
Turner
D.
,
Rupp
R.
,
Hollenberg
S.
,
Zhuang
Y.
,
Lassar
A.
(
1991
)
The myoD gene family: Nodal point during specification of the muscle cell lineage.
Science
251
,
761
766
Weintraub
H.
,
Tapscott
S. J.
,
Davis
R. L.
,
Thayer
M. J.
,
Adam
M. A.
,
Lassar
A. B.
,
Miller
A. D.
(
1989
)
Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD.
Proc. Natl. Acad. Sci. USA
86
,
5434
5438
White
N. K.
,
Bonner
P. H.
,
Nelson
D. R.
,
Hauschka
S. D.
(
1975
)
Clonal analyis of vertebrate myogenesis: Medium-dependent classification of colony-forming cells.
Dev. Biol
44
,
346
361
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