Undifferentiated embryonic mesenchymal cells are round/cuboidal in shape. During development, visceral myogenesis is shortly preceded by mesenchymal cell elongation. To determine the role of the cell's shape on smooth muscle development, undifferentiated embryonic mesenchymal cells from intestine (abundant visceral muscle), lung (some visceral muscle) or kidney (no visceral muscle) were plated under conditions that maintained cell rounding or promoted elongation. Regardless of their fate in vivo, all the cells differentiated into smooth muscle upon elongation as indicated by the expression of smooth muscle-specific proteins and the development of membrane potentials of −60 mV and voltage-dependent Ca2+ currents, characteristic of excitable cells. Smooth muscle differentiation occurred within 24 hours and was independent of cell proliferation. Regardless of their fate in vivo, all the round cells remained negative for smooth muscle markers, had membrane potentials of −30 mV and showed no voltage-activated current. These cells, however, differentiated into smooth muscle upon elongation. The role of the cell's shape in controlling smooth muscle differentiation was not overcome by treatment with retinoic acid, TGF-beta1, PDGF BB or epithelial-conditioned medium (all modulators of smooth muscle differentiation). These studies suggest that the mesenchymal cell shape plays a main role in visceral myogenesis.

Reference

Baskin
L. S.
,
Hayward
S. W.
,
Young
P.
,
Cunha
G. R.
(
1996
)
Role of mesenchymal-epithelial interactions in normal bladder development.
J. Urol
156
,
1820
1827
Blank
R. S.
,
Swartz
E. A.
,
Thompson
M. M.
,
Olson
E. N.
,
Owens
G. K.
(
1995
)
A retinoic acid-induced clonal cell line derived from multipotential P19 embryonal carcinoma cells express smooth muscle characteristics.
Circ. Res
76
,
742
749
Chen
C. S.
,
Mrksich
M.
,
Huang
S.
,
Whitesides
G. M.
,
Ingber
D. E.
(
1997
)
Geometric control of cell life and death.
Science
276
,
1425
1428
Cunha
G. R.
,
Battle
E.
,
Young
P.
,
Brody
J.
,
Donjacour
A.
,
Hayashi
N.
,
Kinbara
H.
(
1992
)
Role of epithelial-mesenchymal interactions in the differentiation and spatial organization of visceral smooth muscle.
Epi. Cell Biol
1
,
76
83
Desmouliere
A.
,
Genioz
A.
,
Gabbiani
F.
,
Gabbiani
G.
(
1993
)
Transforming growth factor-1 induces -smooth muscle cell actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts.
J. Cell Biol
122
,
103
111
Duluc
I.
,
Freund
J.-N.
,
Lweberquier
C.
,
Kedinger
M.
(
1994
)
Fetal endoderm primarily holds the temporal and positional information required for mammalian intestinal development.
J. Cell Biol
126
,
211
221
Hirschi
K. K.
,
Rohovsky
S. A.
,
D'Amore
P. A.
(
1998
)
PDGF, TGF-and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate.
J. Cell Biol
141
,
805
814
Holycross
B. J.
,
Blank
R. S.
,
Thompson
M. M.
,
Peach
M. J.
,
Owens
G. K.
(
1992
)
Platelet-derived growth factor-BB-induced expression of smooth muscle differentiation.
Circ. Res
6
,
1525
1532
Kedinger
M.
,
Simon-Assmann
P.
,
Bouziges
F.
,
Arnold
C.
,
Alexandre
E.
,
Haffen
K.
(
1990
)
Smooth muscle actin expression during rat gut development and induction in fetal skin fibroblastic cells associated with intestinal embryonic epithelium.
Differentiation
43
,
87
97
Kheradmand
F.
,
Werner
E.
,
Tremble
P.
,
Symons
M.
,
Werb
Z.
(
1998
)
Role of Rac 1 and oxygen radicals in collagenase-1 expression induced by cell shape change.
Science
280
,
898
902
Li
L.
,
Miano
J. M.
,
Cserjesi
P.
,
Olson
E. N.
(
1996
)
SM22, a marker of adult smooth muscle, is expressed in multiple myogenic lineages during embryogenesis.
Circ. Res
78
,
188
195
McHugh
K.
(
1995
)
Molecular analysis of smooth muscle development in the mouse.
Dev. Dyn
204
,
278
290
Miano
J. M.
,
Cserjesi
P.
,
Ligon
K. L.
,
Periasamy
M.
,
Olson
E. N.
(
1994
)
Smooth muscle myosin heavy chain exclusively marks the smooth muscle lineage during mouse embryogenesis.
Circ. Res
75
,
803
812
Miano
J. M.
,
Olson
E. N.
(
1996
)
Expression of the smooth muscle calponin gene marks the early cardiac and smooth muscle cell lineages during mouse embryogenesis.
J. Biol. Chem
271
,
7095
7103
Mitchell
J. J.
,
Reynolds
S. E.
,
Leslie
K. O.
,
Low
R. B.
,
Woodcock-Mitchell
J.
(
1990
)
Smooth muscle markers in developing rat lung.
Am. J. Respir. Cell Mol. Biol
3
,
515
523
Orlani
A.
,
Ropraz
P.
,
Gabbiani
G.
(
1994
)
Proliferative activity and-smooth muscle actin expression in cultured rat aortic smooth muscle cells are differently modulated by transforming growth factor- 1 and heparin.
Exp. Cell Res
214
,
528
536
Price
L. S.
,
Leng
J.
,
Schwartz
M. A.
,
Bokoch
G. M.
(
1998
)
Activation of Rac and Cdc42 by integrins mediates cell spreading.
Mol. Biol. Cell
9
,
1863
1871
Przywara
D. A.
,
Bhave
S. V.
,
Bhave
A.
,
Wakade
T. D.
,
Wakade
A. R.
(
1991
)
Dissociation between intracellular Ca2+and modulation of [3H]noradrenaline release in chick sympathetic neurons.
J. Physiol. (Lond.)
437
,
201
220
Roman
J.
,
McDonald
J. A.
(
1992
)
Expression of fibronectin, the integrin5 and -smooth muscle actin in heart and lung development.
Am. J. Respir. Mol. Biol
6
,
472
480
Rosette
C.
,
Karin
M.
(
1995
)
Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-kappa B.
J. Cell Biol
128
,
1111
1119
Ruzicka
D.
,
Schwartz
R.
(
1988
)
Sequential activation of-actin genes during avian cardiogenesis: vascular smooth muscle -actin gene transcriptsmark the onset of cardiomyocyte differentiation.
J. Cell Biol
107
,
2575
2586
Sawtell
N.
,
Lessard
J.
(
1989
)
Cellular distribution of smooth muscle actins during mammalian embryogenesis: expression of the-vascular but not the -enteric isoform in differentiating striated myocytes.
J. Cell Biol
109
,
2929
2937
Schiaepfer
D. D.
,
Hanks
S. K.
,
Hunter
T.
,
van der Geer
P.
(
1994
)
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.
Nature
372
,
22
29
Schuger
L.
,
Varani
J.
,
Mitra
J.
,
Gilbride
K.
(
1993
)
Retinoic acid stimulates mouse lung development by a mechanism involving epithelial-mesenchymal interaction and regulation of epidermal growth factor receptors.
Dev. Biol
159
,
462
473
Schuger
L.
,
Skubitz
A. P. N.
,
Zhang
J.
,
Sorokin
L.
,
He
L.
(
1997
)
Laminin1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.
J. Cell Biol
139
,
553
562
Serini
G.
,
Bochaton-Piallat
M.-L.
,
Ropraz
P.
,
Geinoz
A.
,
Borsi
L.
,
Zardi
L.
,
Gabbiani
J.
(
1998
)
The fibronectin domain ED-A is crucial for myoblastic phenotype induction by transforming growth factor-1.
J. Cell Biol
142
,
873
881
Wang
N.
,
Butler
J. P.
,
Ingber
D. E.
(
1993
)
Mechanotransduction across the cell surface and through the cytoskeleton.
Science
260
,
1124
1127
Woodcock-Mitchell
J.
,
White
S.
,
Stirewalt
W.
,
Periasamy
M.
,
Mitchell
J.
,
Low
R. B.
(
1993
)
Myosin isoform expression in developing and remodeling rat lung.
Am. J. Respir. Cell Mol. Biol
8
,
617
625
Yang
Y.
,
Palmer
K. C.
,
Diglio
C.
,
Schuger
L.
(
1998
)
Role of laminin polymerization at the epithelial-mesenchymal interface in bronchial myogenesis.
Development
125
,
2621
2629
Zhu
X.
,
Assoian
R. K.
(
1995
)
Integrin-dependent activation of MAP kinase: A link to shape-dependent cell proliferation.
Mol. Biol. Cell
6
,
273
282
This content is only available via PDF.