Molecular analysis of the cadherin-catenin complex elucidated the central role of beta-catenin in this adhesion complex, as it binds to the cytoplasmic domain of E-cadherin and to alpha-catenin. beta-Catenin may also function in signalling pathways, given its homology to the gene product of the Drosophila segment polarity gene armadillo, which is known to be involved in the wingless signalling cascade. To study the function of beta-catenin during mouse development, gene knock-out experiments were performed in embryonic stem cells and transgenic mice were generated. beta-Catenin null-mutant embryos formed blastocysts, implanted and developed into egg-cylinder-stage embryos. At day 7 post coitum, the development of the embryonic ectoderm was affected in mutant embryos. Cells detached from the ectodermal cell layer and were dispersed into the proamniotic cavity. No mesoderm formation was observed in mutant embryos. The development of extraembryonic structures appeared less dramatically or not at all affected. Our results demonstrate that, although beta-catenin is expressed rather ubiquitously, it is specifically required in the ectodermal cell layer.
Reference
Aberle
H.
, Butz
S.
, Stappert
J.
, Weissig
H.
, Kemler
R.
, Hoschuetzky
H.
(1994
) Assembly of the cadherin-catenin complex in vitro with recombinant proteins.
J. Cell Sci
107
, 3655
–3663
Bradley
R.S.
, Cowin
P.
, Brown
A.M.
(1993
) Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.
J. Cell Biol
123
, 1857
–1865
Butz
S.
, Kemler
R.
(1994
) Distinct cadherin-catenin complexes in Ca2+-dependent cell-cell adhesion.
FEBS Lett
355
, 195
–200
Cowin
P.
, Kapprell
H.P.
, Franke
W.W.
, Tamkun
J.
, Hynes
R.O.
(1986
) Plakoglobin: a protein common to different kinds of intercellular adhesive junctions.
Cell
46
, 1063
–1073
Fagotto
F.
, Gumbiner
B.M.
(1994
) -catenin localization during Xenopus embryogenesis: accumulation at tissue and somite boundaries.
Development
120
, 3667
–3679
Felthaus
J.
, Haegel
H.
, Larue
L.
(1994
) Fast screening of mouse mutants generated after homologous recombination.
Nucleic Acids Res
22
, 5504
–5505
Fleming
T.P.
, Garrod
D. R.
, Elsmore
A. J.
(1991
) Desmosome biogenesis in the mouse preimplantation embryo.
Development
112
, 527
–539
Franke
W.W.
, Goldschmidt
M.D.
, Zimbelmann
R.
, Mueller
H.M.
, Schiller
D.L.
, Cowin
P.
(1989
) Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein.
Biochemistry
86
, 4027
–4031
Friedrich
G.
, Soriano
P.
(1991
) Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice.
Genes Dev
5
, 1513
–1523
Funayama
N.
, Fagotto
F.
, McCrea
P.
, Gumbiner
B.M.
(1995
) Embryonic axis induction by the armadillo repeat domain of-catenin: evidence for intracellular signaling.
J. Cell Biol
128
, 959
–968
Guillemot
F.
, Nagy
A.
, Auerbach
A.
, Rossant
J.
, Joyner
A.L.
(1994
) Essential role of Mash-2 in extraembryonic development.
Nature
371
, 333
–336
Hatzfeld
M.
, Krisjansson
G.I.
, Plessmann
U.
, Weber
K.
(1994
) Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family.
J. Cell Sci
107
, 2259
–2270
Heasman
J.
, Crawford
A.
, Goldstone
K.
, Garner-Hamrick
P.
, Gumbiner
B.
, McCrea
P.
, Kintner
C.
, Yoshida Noro
C.
, Wylie
C.
(1994
) Overexpression of cadherins and underexpression of-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
Cell
79
, 791
–803
Hinck
L.
, Nelson
W.J.
, Papkoff
J.
(1994
) Wnt-1 modulates cell-cell adhesion by stabilizing-catenin binding to the cell adhesion molecule cadherin.
J. Cell Biol
124
, 729
–741
Hinck
L.
, Näthke
I.S.
, Papkoff
J.
, Nelson
W.J.
(1994
) Dynamics of cadherin-catenin complex formation: novel protein interactions and pathways of complex assembly.
J. Cell Biol
125
, 1327
–1340
Hoschuetzky
H.
, Aberle
H.
, Kemler
R.
(1994
) -catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor.
J. Cell Biol
127
, 1375
–1380
Jostarndt
K.
, Puntschart
A.
(1994
) The use of 33P-labelled riboprobes for in situ hybridizations: localization of myosin alkali light-chain mRNAs in adult human skeletal muscle.
Histochemical J
26
, 32
–40
Kawanishi
J.
, Kato
J.
, Sasaki
K.
, Fuji
S.
, Watanabe
N.
, Niitsu
Y.
(1995
) Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the-catenin gene in a human cancer cell line, HSC-39.
Mol. Cell. Biol
15
, 1175
–1181
Kinzler
K.W.
, Nilbert
M.C.
, Su
L.
, Vogelstein
B.
, Bryan
T.M.
, Levy
D.B.
, Smith
K.
, Preisinger
A.C.
, Hedge
P.
, McKechnie
D.
, Finniear
R.
, Markham
A.
, Groeffen
J.
, Boguski
M.S.
, Alstshul
S.F.
, Horii
A.
, Ando
H.
, Miyoshi
Y.
, Miki
Y.
, Nishisho
I.
, Nakamura
Y.
(1991
) Identification of FAP Locus Genes from Chromosome 5q21.
Science
253
, 661
–665
Knudsen
K.
, Wheelock
M.J.
(1992
) Plakoglobin, or an 83-kD homologue distinct from-catenin, interacts with E-cadherin and N-cadherin.
J. Cell Biol
118
, 671
–679
Larue
L.
, Ohsugi
M.
, Hirchenhain
J.
, Kemler
R.
(1994
) E-Cadherin-null mutant embryos fail to form a trophectoderm epithelium.
Proc. Natl. Acad. Sci. USA
91
, 8263
–8267
McMahon
A.P.
, Bradley
A.
(1990
) The Wnt-1 (int-1) protooncogene is required for development of a large region of the mouse brain.
Cell
62
, 1073
–1085
Mountford
P.S.
, Smith
A.G.
(1995
) Internal ribosome entry sites and dicistronic RNAs in mammalian transgenesis.
Trends Genet
11
, 179
–184
Nagafuchi
A.
, Takeichi
M.
(1989
) Transmembrane control of cadherin-mediated cell-cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin.
Cell Regul
1
, 37
–44
Nagy
A.
, Rossant
J.
, Nagy
R.
, Abramow-Newerly
W.
, Roder
J.C.
(1993
) Derivation of completely cell culture-derived mice from early passage embryonic stem cells.
Proc. Nat. Acad. Sci. USA
90
, 8424
–8428
Noordemeer
J.
, Klingensmith
J.
, Perrimon
N.
, Nusse
R.
(1994
) dishevelled and armadillo act in the Wingless signaling pathway in Drosophila.
Nature
367
, 80
–83
Nose
A.
, Takeichi
M.
(1986
) A novel cadherin cell adhesion molecule: its expression pattern associated with implantation and organogenesis of mouse embryos.
J. Cell Biol,
103
, 2649
–2658
Oh
S.K.
, Sarnow
P.
(1993
) Gene regulation: translational initiation by internal ribosome binding.
Curr. Op. Genet. Dev
3
, 295
–300
Oyama
T.
, Kanai
I.
, Ochiai
A.
, Akimoto
S.
, Oda
T.
, Yanagihara
K.
, Nagafuchi
A.
, Tsukita
S.
, Shibamoto
S.
, Ito
F.
, Takeichi
M.
, Matsuda
H.
, Hirohashi
S.
(1994
) A truncated-catenin disrupts the interaction between E-cadherin and -catenin: A cause of loss of intercellular adhesiveness in human cancer cell lines.
Cancer Res
54
, 6282
–6287
Ozawa
M.
, Baribault
H.
, Kemler
R.
(1989
) The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species.
EMBO J
8
, 1711
–1717
Ozawa
M.
, Kemler
R.
(1992
) Molecular organization of the uvomorulin-catenin complex.
J. Cell Biol
116
, 989
–996
Peifer
M.
, McCrea
P.D.
, Green
K.J.
, Wieschaus
E.
, Gumbiner
B.M.
(1992
) The vertebrate adhesive junction proteins-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.
J. Cell Biol
118
, 681
–691
Peifer
M.
, Berg
S.
, Reynolds
A.B.
(1994
) A repeating amino acid motif shared by proteins with diverse cellular roles.
Cell
76
, 789
–791
Peifer
M.
, Sweeton
D.
, Casey
M.
, Wieschaus
E.
(1994
) Wingless signal and zest-white-3 kinase trigger opposite changes in the intracellular distribution of Armadillo.
Development
120
, 369
–380
Pelletier
J.
, Sonenberg
N.
(1988
) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from Poliovirus RNA.
Nature
334
, 320
–325
Reynolds
A.B.
, Daniel
J.
, McCrea
P.
, Wheelock
M.J.
, Wu
J.
, Zhang
Z.
(1994
) Identification of a new catenin: the tyrosine kinase substrate p120rasassociates with E-cadherin complexes.
Mol. Cell. Biol
12
, 8333
–8342
Riggleman
B.
, Schedl
P.
, Wieschaus
E.
(1990
) Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless.
Cell
63
, 549
–560
Rubinfeld
B.
, Souza
B.
, Albert
I.
, Muller
O.
, Chamberlain
S.H.
, Masiarz
F.
, Munemitsu
S.
, Polaris
P.
(1993
) Association of the APC gene product with-catenin.
Science
262
, 1731
–1734
Schneider
S.
, Herrenknecht
K.
, Butz
S.
, Kemler
R.
, Hausen
P.
(1993
) Catenins in Xenopus embryogenesis and their relation to the cadherin-mediated cell-cell adhesion system.
Development
118
, 629
–640
Simeone
A.
, Acampora
D.
, Mallamaci
A.
, Stornaiuolo
A.
, D'Apice
M.R.
, Nigro
V.
, Boncinelli
E.
(1993
) A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.
EMBO J
12
, 2735
–2747
Smith
A.G.
, Hooper
M.L.
(1987
) Buffalo Rat Liver cells produce a diffusible activitity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells.
Dev. Biol
121
, 1
–9
Spindle
A.
(1980
) An improved culture medium for mouse blastocysts.
In Vitro
16
, 669
–674
Su
L. K.
, Vogelstein
B.
, Kinzler
K.
(1993
) Association of the APC tumor suppressor protein with catenins.
Science
262
, 1734
–1737
Takeichi
M.
(1991
) Cadherin cell adhesion molecules as a morphogenetic regulator.
Science
251
, 1451
–1455
Vestweber
D.
, Kemler
R.
(1984
) Rabbit antiserum against a purified surface glycoprotein decompacts mouse preimplantation embryos and reacts with specific adult tissues.
Exp. Cell Res
152
, 169
–178
Vestweber
D.
, Kemler
R.
(1985
) Identification of a putative cell adhesion domain of uvomorulin.
EMBO J
4
, 3393
–3398
Wilkinson
D. G.
, Bhatt
S.
, Herrmann
B.
(1990
) Expression pattern of the mouse T gene and its role in mesoderm formation.
Nature
343
, 657
–659
Yamamura
H.
, Spindle
A.
(1988
) Stage-specific response of preimplantation mouse embryos to W-7, a calmodulin antagonist.
J. Exp. Zool
248
, 45
–54
Yano
R.
, Oakes
M.
, Yamaghishi
M.
, Dodd
J.A.
, Nomura
M.
(1992
) Cloning and characterization of SPR1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae.
Mol. Cell. Biol
12
, 5640
–5651
This content is only available via PDF.
© 1995 by Company of Biologists
1995
