Rho GTPases and cadherin-based cell adhesion in skeletal muscle development.
ABSTRACT The small GTPases of the Rho subfamily (RhoA, Rac1 and Cdc42) are signaling molecules involved in cytoskeleton remodeling and gene transcription. Their activities are important for many cellular processes, including myogenesis. Classical cadherin adhesion molecules are key determinants of cell recognition and tissus morphogenesis and act as adhesion-activated signaling receptors. Rho GTPases have emerged as key mediators of their activity. Not only signal transduction pathways link cadherins to Rho GTPases but also Rho GTPases to cadherins. We focus in this review on the role of cadherins and Rho GTPases in normal myogenesis as well as in pathological development of rhabdomyosarcoma.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: Dysferlin deficiency causes limb-girdle muscular dystrophy type 2B (LGMD2B; proximal weakness) and Miyoshi myopathy (distal weakness). Muscle inflammation is often present in dysferlin deficiency, and patients are frequently misdiagnosed as having polymyositis. Because monocytes normally express dysferlin, we hypothesized that monocyte/macrophage dysfunction in dysferlin-deficient patients might contribute to disease onset and progression. We therefore examined phagocytic activity, in the presence and absence of cytokines, in freshly isolated peripheral blood monocytes from LGMD2B patients and in the SJL dysferlin-deficient mouse model. Dysferlin-deficient monocytes showed increased phagocytic activity compared with control cells. siRNA-mediated inhibition of dysferlin expression in the J774 macrophage cell line resulted in significantly enhanced phagocytosis, both at baseline and in response to tumor necrosis factor-alpha. Immunohistochemical analysis revealed positive staining for several mononuclear cell activation markers in LGMD2B human muscle and SJL mouse muscle. SJL muscle showed strong up-regulation of endocytic proteins CIMPR, clathrin, and adaptin-alpha, and LGMD2B muscle exhibited decreased expression of decay accelerating factor, which was not dysferlin-specific. We further showed that expression levels of small Rho family GTPases RhoA, Rac1, and Cdc 42 were increased in dysferlin-deficient murine immune cells compared with control cells. Therefore, we hypothesize that mild myofiber damage in dysferlin-deficient muscle stimulates an inflammatory cascade that may initiate, exacerbate, and possibly perpetuate the underlying myofiber-specific dystrophic process.American Journal Of Pathology 04/2008; 172(3):774-85. · 4.52 Impact Factor
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ABSTRACT: Obscurin is a large ( approximately 800-kDa), modular protein of striated muscle that concentrates around the M-bands and Z-disks of each sarcomere, where it is well positioned to sense contractile activity. Obscurin contains several signaling domains, including a rho-guanine nucleotide exchange factor (rhoGEF) domain and tandem pleckstrin homology domain, consistent with a role in rho signaling in muscle. We investigated the ability of obscurin's rhoGEF domain to interact with and activate small GTPases. Using a combination of in vitro and in vivo approaches, we found that the rhoGEF domain of obscurin binds selectively to rhoA, and that rhoA colocalizes with obscurin at the M-band in skeletal muscle. Other small GTPases, including rac1 and cdc42, neither associate with the rhoGEF domain of obscurin nor concentrate at the level of the M-bands. Furthermore, overexpression of the rhoGEF domain of obscurin in adult skeletal muscle selectively increases rhoA expression and activity in this tissue. Overexpression of obscurin's rhoGEF domain and its effects on rhoA alter the expression of rho kinase and citron kinase, both of which can be activated by rhoA in other tissues. Injuries to rodent hindlimb muscles caused by large-strain lengthening contractions increases rhoA activity and displaces it from the M-bands to Z-disks, similar to the effects of overexpression of obscurin's rhoGEF domain. Our results suggest that obscurin's rhoGEF domain signals at least in part by inducing rhoA expression and activation, and altering the expression of downstream kinases in vitro and in vivo.Molecular biology of the cell 08/2009; 20(17):3905-17. · 5.98 Impact Factor
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ABSTRACT: Epigenetic regulation, including DNA methylation, plays an important role in several differentiation processes and possibly in adipocyte differentiation. To search for genes that show methylation change during adipogenesis, genome-wide DNA methylation analysis in insulin-induced adipogenesis of 3T3-L1 preadipocyte cells was performed using a method called microarray-based integrated analysis of methylation by isoschizomers (MIAMI). The MIAMI revealed that Hpa II sites of exon 1 in a Rho guanine nucleotide exchange factor 19 (ARHGEF19; WGEF) gene were demethylated during adipocyte differentiation of 3T3-L1 cells. Deletion of the region containing cytosine-guanine (CpG) sites that showed methylation change suppressed transcriptional activity in the reporter assay, indicating that this region regulates WGEF transcription. WGEF expression in 3T3-L1 cells was reduced during adipocyte differentiation, and high-fat diet-induced obese mice also showed lower expression of WGEF gene than control mice in white adipose tissue. Additionally, forced expression of WGEF in 3T3-L1 cells down-regulated the expression of adipogenic marker genes and inhibited the adipogenic program. This study clarified that adipogenesis was regulated by WGEF expression through DNA methylation change.PLoS ONE 02/2009; 4(6):e5809. · 3.73 Impact Factor
Rho GTPases and cadherin-based cell adhesion in skeletal muscle development
SOPHIE CHARRASSE, MARIE CAUSERET, FRANCK COMUNALE, ARMELLE BONET-KERRACHE
and CE´CILE GAUTHIER-ROUVIE`RE*
CRBM – CNRS, 1919 Route de Mende, 34293 Montpellier Cedex, France
The small GTPases of the Rho subfamily (RhoA, Rac1 and Cdc42) are signaling molecules involved in cytoskeleton
remodeling and gene transcription. Their activities are important for many cellular processes, including myogenesis.
Classical cadherin adhesion molecules are key determinants of cell recognition and tissus morphogenesis and act as
adhesion-activated signaling receptors. Rho GTPases have emerged as key mediators of their activity. Not only
signal transduction pathways link cadherins to Rho GTPases but also Rho GTPases to cadherins. We focus in this
review on the role of cadherins and Rho GTPases in normal myogenesis as well as in pathological development of
In vertebrates, skeletal muscle starts to form in the
embryonic life from paraxial mesoderm which segments
into somites, epithelial structures that flank the neural
tube and the notochord. The ventral portion of the
somite, the sclerotome, will give rise to the axial skeleton
whereas its dorsal portion, the dermomyotome, will give
rise to the derm and to the skeletal muscles of the body
and the limbs (Figure 1) (Buckingham, 2001; Pownall
et al., 2002; Buckingham et al., 2003). Whereas body
muscles are entirely derived from the somites, head
muscles develop from paraxial and prechordal meso-
derm. This first step, called specification, is controled by
signaling molecules, such as Sonic Hedgehog (Shh) and
Wnt proteins coming from the dorsal neural tube which
drive the expression of the myogenic determination
genes Myf5 and MyoD. In addition, negative regulation
by proteins such as BMP4, released by the lateral
mesoderm, or proteins of the transforming growth
factor b (TGFb) and fibroblast growth factor (FGF)
families play an important role in this process (Massa-
gue et al., 1986; Olson et al., 1986; Pourquie et al.,
1996). The two basic helix-loop-helix transcription
factors Myf5 and MyoD play a critical role during the
differentiation process as in double Myf5/MyoD mu-
tants no skeletal muscle forms due to the absence of
myoblast precursors (Rudnicki et al., 1993). After this
specification step, myoblast delaminate, migrate and
proliferate until their reach their sites of differentiation.
The scatter factor (HGF) and its receptor c-met, are
involved in the delamination and migration processes
(Dietrich et al., 1999). The homeo-domain containing
transcription factors Pax3 and Lbx1 are also implicated
in the migration of cells from the somite (Buckingham
et al., 2003). One remarkable aspect of this process is
that some muscle precursor cells, for instance those of
the limb and tongue muscles, have to undergo long
migration before differentiating at their target sites. In
this case, the cells express Myf5 and MyoD only when
they reach the limb (Tajbakhsh and Buckingham, 1994).
Then myoblasts, through the action of a variety of
muscle-specific transcription factors such as member of
the MyoD, Mef2 and homeo-domain families, differen-
tiate and fuse into myotubes to finally maturate into
muscle fibers. Two successive waves of fusion called
primary and secondary myogenesis arise giving the
primary fiber and secondary fiber. These two types of
fibers will become the slow and the fast fibers respec-
tively. Finally, another population of quiescent myo-
blast, called satellite cells, is located along the muscle
fiber. These muscle cells, which origin is unclear, become
activated to divide and differentiate in response to
muscle damage (Buckingham et al., 2003).
In addition to diffusible molecules (growth factors,
morphogens,…), the interaction of muscle cell precur-
sors with their neighbors and with the extracellular
matrix, is also involved in the regulation of myogenesis.
In this review, we focus on the role of the Ca2+-
dependent cell–cell adhesion molecule of the cadherin
family. Cadherins, which act as adhesion receptors
inducing signaling cascades in particular through the
regulation of Rho GTPases activity, coordinate myo-
genesis with growth factors (Knudsen, 1990). Some-
differentiation of skeletal muscle precursor cells give
rise to rhabdomyosarcomas, tumors of childhood of
skeletal muscle origin (Merlino and Helman, 1999).
Potential deregulation in cadherin-mediated adhesion
of the growthand
* To whom correspondence should be addressed: Tel.: þ33-
467613355; Fax: þ33467521559; E-mail: email@example.com
Journal of Muscle Research and Cell Motility 24: 309–313, 2003.
? 2003 Kluwer Academic Publishers. Printed in the Netherlands.
and Rho GTPases activation could lead to problems in
the growth arrest and the myogenic program engage-
ment, thus favoring formation of rhabdomyosarcoma.
Cadherin-based cell adhesion regulates myogenesis
Cadherins are homophilic cell–cell adhesion molecules
essential for the organization of cells into tissues during
embryonic development. They are also involved in cell
growth, migration and differentiation. Cadherins are
highly conserved transmembrane glycoproteins that
mediate homotypic cell–cell adhesion through their
extracellular domain. Cadherin cytoplasmic domains
provide F-actin cytoskeleton attachment points through
association of catenins and other cytoskeletal associated
proteins (Kemler, 1993). These adhesive receptors are
likely to regulate diverse functions beyond the basic
adhesive process including intracellular signaling events
(Fukata and Kaibuchi, 2001). Developing skeletal mus-
cle expresses N-, M-, R- and 11-cadherin and cadherin-
dependent adhesion is required for a variety of cellular
events (Figure 1) (Knudsen, 1990). Cadherin-11 is only
weakly expressed in developing muscles and is mainly
found in mesenchymal cells in the distal portion of the
limb and the sclerotome cells in the somites (Kimura
et al., 1995). Cadherin-11 expression is down-regulated
in differentiating structures and is most probably in-
volved in muscle-motoneurons interactions (Padilla
et al., 1998). N-cadherin is expressed early in somites,
the myotome and limb buds, and is down-regulated as
synaptogenesis and secondary myogenesis proceed (Du-
band et al., 1987; Hatta et al., 1987; Linask et al., 1998).
N-cadherin-dependent inter-cellular adhesion has a
major role in cell cycle exit and in the induction of the
skeletal muscle differentiation program (Knudsen et al.,
1990; Mege et al., 1992; George-Weinstein et al., 1997;
Redfield et al., 1997; Goichberg and Geiger, 1998).
Recently, we started to elucidate the signaling pathway
activated dowstream N-cadherin adhesive receptor (see
next paragraph) (Charrasse et al., 2002). M-cadherin is
expressed later than N-cadherin. Its expression increases
at the onset of secondary myogenesis, and this protein
has been implicated in terminal myoblast differentiation,
particularly in myoblast fusion (Zeschnigk et al., 1995).
R-cadherin is detected in the somites and the limbs, and
is localized at cell–cell contacts of primary myoblasts
during primary myogenesis, as well as at the primary
myotube/secondary myoblast boundaries during sec-
ondary myogenesis (Rosenberg et al., 1997). R-cadherin
expression is lost in adult muscles. It is now clear that
cadherins could be true cell surface receptors relaying
signals from the cell environment towards the inside of
the cells. Questions to be answered now include the
identification of the signal transduction pathways eli-
cited by these different cadherin molecules during the
skeletal muscle development process.
Rho GTPases regulates myogenesis
The Rho family of Ras-like GTPases contains 21
members clustered in four subgroups comprising RhoA,
RhoB and RhoC; Rnd1, Rnd2 and Rnd3; RhoBTB1,
RhoBTB2 and RhoBTB3; and Rac1, Rac2, Rac3,
Cdc42, TC10, TCL, RhoG, Chp1 and Chp2/Wrch-1.
Fig. 1. Schematic representation of skeletal muscle formation in vertebrates and cadherin expression during this process. Somites are formed and
mature following a rostrocaudal gradient. Cadherin-11 is found in the somites but its expression is rapidly lost. In contrast, N- and R-cadherin
are expressed all over muscle progenitor migration and myogenesis. M-cadherin is expressed during secondary myogenesis and, with N-cadherin,
is maintained in the adulte.
The remaining proteins (RhoD, Rif and RhoH/TTF)
delineate distinct stems in the tree. GTPases of the Rho
family act as molecular switches that convert extracel-
lular signals into multiple cellular effects. These proteins
act as signaling gates, which switch on when bound to
GTP and switch off when bound to GDP. Although 21
members are known in mammals, only RhoA, Rac1 and
Cdc42 have been studied extensively. These proteins
regulate a variety of cytoskeleton-dependent cell func-
tions as well as gene transcription (Hall, 1998; Fort,
1999). The role of Rho GTPases in myogenesis started
to be studied in 1998 in myogenic cell lines. RhoA, Rac1
and Cdc42 differentially regulate the commitment to-
ward myogenesis (Figure 2). RhoA positively regulates
MyoD expression and skeletal muscle cell differentiation
(Carnac et al., 1998; Takano et al., 1998; Wei et al.,
1998). In contrast, Rac1 does not appear to affect MyoD
activity (Ramocki et al., 1997). Rac1 and Cdc42 play a
dual role in myogenesis. On one hand, inhibition of
Rac1 and Cdc42, through decreasing p38 MAPK
activity, interferes with myogenesis (Meriane et al.,
2002a). On the other hand, expression of constitutively
active forms of Rac1 and Cdc42 inhibits myogenesis
through activation of the c-jun NH2-terminal kinase
(JNK) cascade (Gallo et al., 1999; Meriane et al., 2000).
Evidence that Rho GTPases are involved in the process
of myogenesis during murine embryogenesis was pro-
vided by Trio knockout mice (O’Brien et al., 2000).
Trio is a guanine exchange factor regulating Rho
GTPase’s activity (Bellanger et al., 1998; Blangy et al.,
2000). Rho GTPase activity might be coordinately
controled by various myogenesis regulators. In the
developing embryo, precursor cells migrate from the
dermomyotome to find premuscle masses in the limbs
and elswhere. During this migration process, myogen-
esis is inhibited. Rac1 and Cdc42 regulate migration in
various cell systems (Nobes and Hall, 1995) and are
potent inhibitors of skeletal myogenesis (Meriane et al.,
2000). Thus activation of Rac1 and Cdc42 might play an
important role in both migration and myogenesis
inhibition during development. Interestingly, we have
observed that TGFb, a potent inhibitor of skeletal
myogenesis, activates Rac1 and Cdc42 in myoblasts
(Meriane et al., 2002b). In addition, the myoblast
migrating promoting factor SF/HGF is known to
activate Rho GTPases (Ridley et al., 1995). Beside to
Fig. 2. Schematic view of N-cadherin-mediated adhesion and Rho GTPases activity during myogenesis and in rhabdomyosarcoma. In normal
myoblasts, activation of N-cadherin adhesive receptor deceases the activity of Rac1 and Cdc42 and JNK level, which favor cell cycle exit.
Concomitant increases in RhoA favor (serum response factor) SRF activation which also allows cell cycle exit and muscle-specific genes
expression. Rho GTPase activity also controls the formation and the stabilization of the cadherin-dependent adhesive receptors. In
rhabdomyoblasts, deregulated HGF/SF, TGFb and Ras signaling might be involved in the deregulation of Rho GTPase activity which in turn
could lead to loss of cell–cell adhesion. Once cadherin-dependent cell–cell contacts are perturbed, cytosolic p120 can affect the levels of RhoA,
Rac1 and Cdc42 activation and thus amplify the junction destabilization. Elevated Rac1 and Cdc42 activity inhibits cell cycle exit and myogenesis
induction and favors myoblast transformation.
growth factors, we recently showed that N-cadherin-
mediated adhesion activates RhoA (Figure 2) (Char-
rasse et al., 2002). In the developing embryo, N-cadhe-
rin-mediated RhoA activation might play an important
role during somitogenesis, myotome formation and also
terminal skeletal myogenesis. An attractive function for
RhoA could be to inhibit cell migration and to favor
myogenesis. Further studies will be required to correlate
the activity of Rho GTPases with skeletal myogenesis
during development and in particular to understand
how muscle cadherins could affect Rho GTPases activity
during this process.
Rhabdomyosarcoma, a skeletal muscle pathology
Rhabdomyosarcomas (RMS) are highly malignant tu-
mors of skeletal muscle origin, accounting for 5–10% of
childhood cancers and for more than 50% of pediatric
soft tissue sarcoma (Merlino and Helman, 1999). They
are thought to arise as a consequence of regulatory
disruption of the growth and differentiation of skeletal
muscle precursor cells, hence they show some charac-
teristics of skeletal muscle. Two major subtypes have
been identified based on both histological and molecu-
lar/genetic markers (Scrable et al., 1989). Embryonal
RMS (ERMS) are comprised of spindle shaped cells.
They are characterized by loss of heterozygosity at the
11p15 locus which is associated with loss of maternal
and duplication of parental chromosomal material, as
well as loss of heterozygosity at the chromosome 16
(Visser et al., 1997). Alveolar RMS (ARMS) are com-
prised of small round densely packed cells. They are
characterized by a reciprocal translocation between the
5¢ DNA-binding domain of PAX3 or PAX7, members
of the Paired Box transcription factor family to the
transactivation domain of FKHR, a member of the
forked/HNF-3 transcription factor family (Fredericks
et al., 1995). Other genetic alterations have been de-
scribed in RMS, such as mutations in p53, N-ras and K-
ras and overexpression of N-myc, IGF2 and c-met
(Merlino and Helman, 1999).
Role of cadherin in development of rhabdomyosarcoma
Tumor cells often show a decrease in cell–cell and/or
cell–matrix adhesion and 20–30% of RMS are already
metastasic at the first examination (Sommelet et al.,
1998). Cadherins play an important role in the regula-
tion of growth and migration during cell transforma-
tion. We have observed an aberrant expression of
cadherin/catenin cell–cell adhesion molecules in RMS,
suggesting deficient inter-cellular adhesion. This could
lead to problems in the growth arrest and the myogenic
program engagement, thus favoring cancer develop-
ment. Indeed, we have observed an overall decrease in
the expression of N- and M-cadherins and catenins in
RMS at both the mRNA and protein levels as well as
defects in their localization (Charrasse et al., submit-
ted). Many autocrine loops (EGF, IGF, TGFb, HGF/
SF) are often involved in regulating proliferation and/or
differentiation in transformed cells (El-Badry et al.,
1990; Bouche et al., 2000). In particular, deregulated
HGF/SF, TGFb and Ras signaling have been involved
in the development of RMS and are also involved in the
loss of cell–cell adhesion, leading to aberrant cell
migration and deregulated growth (Ferracini et al.,
1996; Potempa and Ridley, 1998). Further studies will
be required to identify the mechanisms involved in the
decrease in cadherin/catenin expression and their delo-
Role of Rho GTPases in development of
Rho family of small GTPases are critical intracellular
mediators of actin-modelling events that normally con-
trol directional cell migration and adhesion. Conse-
quently, altered cytoskeletal modeling is a likely target
for subversion during oncogenic transformation and
tumor progression with misregulated GTPases. Having
demonstrated that expression of active Rac1 and Cdc42
inhibits skeletal myogenesis, we have further analyzed
whether these GTPases also affect mitogenesis and
proliferation of myoblasts. Indeed, myogenesis involves
withdrawal of myoblasts from the cell cycle, a prerequi-
site for differentiation, activation of muscle-specific gene
expression and myoblasts fusion (Lassar et al., 1994).
We have shown that active Rac1 and Cdc42 expression
impairs cell cycle exit of myoblasts (Meriane et al.,
2002a). Heller et al. also reported that Rac1 inhibits
myogenesis by preventing the withdrawal of myoblasts
from the cell cycle (Heller et al., 2001). In addition,
expression of activated forms of Rac1 and Cdc42 elicits
the loss of cell contact inhibition and anchorage-depen-
dent growth, suggesting that deregulated Rac1 and
Cdc42 might mediate transformation pathways in myo-
blastic cells. Along this line, Rac1 and Cdc42 were found
constitutively activated in RMS-derived cell lines (Mer-
iane et al., 2002b). Again deregulated HGF/SF, TGFb
and Ras signaling might keep activated the Rac1/Cdc42
downstream pathways. Further studies will be required
to determine these molecular mechanisms. Interestingly,
cytosolic p120 can activate Rac1 and Cdc42 resulting in
an altered balance of cellular Rho protein activities that
facilitates cell migration (Anastasiadis et al., 2000;
Noren et al., 2000). In RMS we have observed defects
in p120 expression and localization and further studies
will be necessary to further correlate these defects with
activity of Rho GTPases.
We are grateful to A. Blangy for critical reading of the
manuscript. Research activity was supported by grants
from Association pour la Recherche contre le Cancer,
Ligue contre le Cancer and Association Franc ¸ aise contre
Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford
HC, Zheng Y and Reynolds AB (2000) Nat Cell Biol 2: 637–644.
Bellanger JM, Zugasti O, Lazaro JB, Diriong S, Fernandez A, Lamb N
and Debant A (1998) Oncogene 16: 147–152.
Blangy A, Vignal E, Schmidt S, Debant A, Gauthier-Rouviere C and
Fort P (2000) J Cell Sci 113: 729–739.
Bouche M, Canipari R, Melchionna R, Willems D, Senni MI and
Molinaro M (2000) Faseb J 14: 1147–1158.
Buckingham M (2001) Curr Opin Genet Dev 11: 440–448.
Buckingham M, Bajard L, Chang T, Daubas P, Hadchouel J, Meilhac
S, Montarras D, Rocancourt D and Relaix F (2003) J Anat 202:
Carnac G, Primig M, Kitzmann M, Chafey P, Tuil D, Lamb N and
Fernandez A (1998) Mol Biol Cell 9: 1891–1902.
Charrasse S, Meriane M, Comunale F, Blangy A and Gauthier-
Rouviere C (2002) J Cell Biol 158: 953–965.
Dietrich S, Abou-Rebyeh F, Brohmann H, Bladt F, Sonnenberg-
Riethmacher E, Yamaai T, Lumsden A, Brand-Saberi B and
Birchmeier C (1999) Development 126: 1621–1629.
Duband JL, Dufour S, Hatta K, Takeichi M, Edelman GM and Thiery
JP (1987) J Cell Biol 104: 1361–1374.
El-Badry OM, Minniti C, Kohn EC, Houghton PJ, Daughaday WH
and Helman LJ (1990) Cell Growth Differ 1: 325–331.
Ferracini R, Olivero M, Di Renzo MF, Martano M, De Giovanni C,
Nanni P, Basso G, Scotlandi K, Lollini PL and Comoglio PM
(1996) Oncogene 12: 1697–1705.
Fort P (1999) Prog Mol Subcell Biol 22: 159–181.
Fredericks WJ, Galili N, Mukhopadhyay S, Rovera G, Bennicelli J,
Barr FG and Rauscher FJ 3rd (1995) Mol Cell Biol 15: 1522–
Fukata M and Kaibuchi K (2001) Nat Rev Mol Cell Biol 2: 887–
Gallo R, Serafini M, Castellani L, Falcone G and Alema S (1999) Mol
Biol Cell 10: 3137–3150.
George-Weinstein M, Gerhart J, Blitz J, Simak E and Knudsen KA
(1997) Dev Biol 185: 14–24.
Goichberg P and Geiger B (1998) Mol Biol Cell 9: 3119–3131.
Hall A (1998) Science 279: 509–514.
Hatta K, Takagi S, Fujisawa H and Takeichi M (1987) Dev Biol 120:
Heller H, Gredinger E and Bengal E (2001) J Biol Chem 6: 6.
Kemler R (1993) Trends Genet 9: 317–321.
Kimura Y, Matsunami H, Inoue T, Shimamura K, Uchida N, Ueno T,
Miyazaki T and Takeichi M (1995) Dev Biol 169: 347–358.
Knudsen KA (1990) Curr Opin Cell Biol 2: 902–906.
Knudsen KA, Myers L and McElwee SA (1990) Exp Cell Res 188:
Lassar AB, Skapek SX and Novitch B (1994) Curr Opin Cell Biol 6:
Linask KK, Ludwig C, Han MD, Liu X, Radice GL and Knudsen KA
(1998) Dev Biol 202: 85–102.
Massague J, Cheifetz S, Endo T and Nadal-Ginard B (1986) Proc Natl
Acad Sci USA 83: 8206–8210.
Mege RM, Goudou D, Diaz C, Nicolet M, Garcia L, Geraud G and
Rieger F (1992) J Cell Sci 103: 897–906.
Meriane M, Charrasse S, Comunale F and Gauthier-Rouviere C
(2002a) Biol Cell 94: 535–543.
Meriane M, Charrasse S, Comunale F, Mery A, Fort P, Roux P and
Gauthier-Rouviere C (2002b) Oncogene 21: 2901–2907.
Meriane M, Roux P, Primig M, Fort P and Gauthier-Rouviere C
(2000) Mol Biol Cell 11: 2513–2528.
Merlino G and Helman LJ (1999) Oncogene 18: 5340–5348.
Nobes CD and Hall A (1995) Biochem Soc Trans 23: 456–459.
Noren NK, Liu BP, Burridge K and Kreft B (2000) J Cell Biol 150:
O’Brien SP, Seipel K, Medley QG, Bronson R, Segal R and Streuli M
(2000) Proc Natl Acad Sci USA 97: 12074–12078.
Olson EN, Sternberg E, Hu JS, Spizz G and Wilcox C (1986) J Cell
Biol 103: 1799–1805.
Padilla F, Broders F, Nicolet M and Mege RM (1998) Mol Cell
Neurosci 11: 217–233.
Potempa S and Ridley AJ (1998) Mol Biol Cell 9: 2185–2200.
Pourquie O, Fan CM, Coltey M, Hirsinger E, Watanabe Y, Breant C,
Francis-West P, Brickell P, Tessier-Lavigne M and Le Douarin
NM (1996) Cell 84: 461–471.
Pownall ME, Gustafsson MK and Emerson CP (2002) Annu Rev Cell
Dev Biol 18: 747–783.
Ramocki MB, Johnson SE, White MA, Ashendel CL, Konieczny SF
and Taparowsky EJ (1997) Mol Cell Biol 17: 3547–3555.
Redfield A, Nieman MT and Knudsen KA (1997) J Cell Biol 138:
Ridley AJ, Comoglio PM and Hall A (1995) Mol Cell Biol 15: 1110–
Rosenberg P, Esni F, Sjodin A, Larue L, Carlsson L, Gullberg D,
Takeichi M, Kemler R and Semb H (1997) Dev Biol 187: 55–70.
Rudnicki MA, Schnegelsberg PN, Stead RH, Braun T, Arnold HH
and Jaenisch R (1993) Cell 75: 1351–1359.
Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K and Sapienza
C (1989) Proc Natl Acad Sci USA 86: 7480–7484.
Sommelet D, Pinkerton R, Brunat-Mentigny M, Farsi F, Martel I,
Philip T, Ranchere-Vince D and Thiesse P (1998) Bull Cancer 85:
Tajbakhsh S and Buckingham ME (1994) Proc Natl Acad Sci USA 91:
Takano H, Komuro I, Oka T, Shiojima I, Hiroi Y, Mizuno T and
Yazaki Y (1998) Mol Cell Biol 18: 1580–1589.
Visser M, Sijmons C, Bras J, Arceci RJ, Godfried M, Valentijn LJ,
Voute PA and Baas F (1997) Oncogene 15: 1309–1314.
Wei L, Zhou W, Croissant JD, Johansen FE, Prywes R, Balasubra-
manyam A and Schwartz RJ (1998) J Biol Chem 273: 30287–
Zeschnigk M, Kozian D, Kuch C, Schmoll M and Starzinski-Powitz A
(1995) J Cell Sci 108: 2973–2981.