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Development, Vol 128, Issue 8 1253-1264, Copyright © 2001 by Company of Biologists

JOURNAL ARTICLES

Inactivation of the (&bgr;)-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development

V Brault, R Moore, S Kutsch, M Ishibashi, DH Rowitch, AP McMahon, L Sommer, O Boussadia and R Kemler
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany. kemler@immunbio.mpg.de

('bgr;)-Catenin is a central component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway. We have investigated the role of (&bgr;)-catenin during brain morphogenesis, by specifically inactivating the (&bgr;)-catenin gene in the region of Wnt1 expression. To achieve this, mice with a conditional ('floxed') allele of (&bgr;)-catenin with required exons flanked by loxP recombination sequences were intercrossed with transgenic mice that expressed Cre recombinase under control of Wnt1 regulatory sequences. (&bgr;)-catenin gene deletion resulted in dramatic brain malformation and failure of craniofacial development. Absence of part of the midbrain and all of the cerebellum is reminiscent of the conventional Wnt1 knockout (Wnt1(-)(/)(-)), suggesting that Wnt1 acts through (&bgr;)-catenin in controlling midbrain-hindbrain development. The craniofacial phenotype, not observed in embryos that lack Wnt1, indicates a role for (&bgr;)-catenin in the fate of neural crest cells. Analysis of neural tube explants shows that (&bgr;)-catenin is efficiently deleted in migrating neural crest cell precursors. This, together with an increased apoptosis in cells migrating to the cranial ganglia and in areas of prechondrogenic condensations, suggests that removal of (&bgr;)-catenin affects neural crest cell survival and/or differentiation. Our results demonstrate the pivotal role of (&bgr;)-catenin in morphogenetic processes during brain and craniofacial development.
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T. Ohyama, O. A. Mohamed, M. M. Taketo, D. Dufort, and A. K. Groves
Wnt signals mediate a fate decision between otic placode and epidermis
Development, March 1, 2006; 133(5): 865 - 875.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
A. L. Evans and P. J. Gage
Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development
Hum. Mol. Genet., November 15, 2005; 14(22): 3347 - 3359.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
L. C. Murtaugh, A. C. Law, Y. Dor, and D. A. Melton
{beta}-Catenin is essential for pancreatic acinar but not islet development
Development, November 1, 2005; 132(21): 4663 - 4674.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T. Gaur, C. J. Lengner, H. Hovhannisyan, R. A. Bhat, P. V. N. Bodine, B. S. Komm, A. Javed, A. J. van Wijnen, J. L. Stein, G. S. Stein, et al.
Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
J. Biol. Chem., September 30, 2005; 280(39): 33132 - 33140.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
K. Grobe, M. Inatani, S. R. Pallerla, J. Castagnola, Y. Yamaguchi, and J. D. Esko
Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function
Development, August 15, 2005; 132(16): 3777 - 3786.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. L. Holmen, C. R. Zylstra, A. Mukherjee, R. E. Sigler, M.-C. Faugere, M. L. Bouxsein, L. Deng, T. L. Clemens, and B. O. Williams
Essential Role of {beta}-Catenin in Postnatal Bone Acquisition
J. Biol. Chem., June 3, 2005; 280(22): 21162 - 21168.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
H. Lickert, B. Cox, C. Wehrle, M. M. Taketo, R. Kemler, and J. Rossant
Dissecting Wnt/{beta}-catenin signaling during gastrulation using RNA interference in mouse embryos
Development, June 1, 2005; 132(11): 2599 - 2609.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
H.-M. I. Yu, B. Jerchow, T.-J. Sheu, B. Liu, F. Costantini, J. E. Puzas, W. Birchmeier, and W. Hsu
The role of Axin2 in calvarial morphogenesis and craniosynostosis
Development, April 15, 2005; 132(8): 1995 - 2005.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
H. Wurdak, L. M. Ittner, K. S. Lang, P. Leveen, U. Suter, J. A. Fischer, S. Karlsson, W. Born, and L. Sommer
Inactivation of TGF{beta} signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome
Genes & Dev., March 1, 2005; 19(5): 530 - 535.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
H. Hu, M. J. Hilton, X. Tu, K. Yu, D. M. Ornitz, and F. Long
Sequential roles of Hedgehog and Wnt signaling in osteoblast development
Development, January 1, 2005; 132(1): 49 - 60.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
W. N. de Vries, A. V. Evsikov, B. E. Haac, K. S. Fancher, A. E. Holbrook, R. Kemler, D. Solter, and B. B. Knowles
Maternal {beta}-catenin and E-cadherin in mouse development
Development, September 15, 2004; 131(18): 4435 - 4445.
[Abstract] [Full Text] [PDF]

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 JCBHome page
S. Liebner, A. Cattelino, R. Gallini, N. Rudini, M. Iurlaro, S. Piccolo, and E. Dejana
{beta}-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse
J. Cell Biol., August 2, 2004; 166(3): 359 - 367.
[Abstract] [Full Text] [PDF]

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 J. Clin. Pathol.Home page
M A Dyer
Mouse models of childhood cancer of the nervous system
J. Clin. Pathol., June 1, 2004; 57(6): 561 - 576.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
H. Akiyama, J. P. Lyons, Y. Mori-Akiyama, X. Yang, R. Zhang, Z. Zhang, J. M. Deng, M. M. Taketo, T. Nakamura, R. R. Behringer, et al.
Interactions between Sox9 and {beta}-catenin control chondrocyte differentiation
Genes & Dev., May 1, 2004; 18(9): 1072 - 1087.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
R. W. Stottmann, M. Choi, Y. Mishina, E. N. Meyers, and J. Klingensmith
BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium
Development, May 1, 2004; 131(9): 2205 - 2218.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
J. L. Lewis, J. Bonner, M. Modrell, J. W. Ragland, R. T. Moon, R. I. Dorsky, and D. W. Raible
Reiterated Wnt signaling during zebrafish neural crest development
Development, March 15, 2004; 131(6): 1299 - 1308.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
H.-Y. Lee, M. Kleber, L. Hari, V. Brault, U. Suter, M. M. Taketo, R. Kemler, and L. Sommer
Instructive Role of Wnt/{beta}-Catenin in Sensory Fate Specification in Neural Crest Stem Cells
Science, February 13, 2004; 303(5660): 1020 - 1023.
[Abstract] [Full Text] [PDF]

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 JEMHome page
M. Cobas, A. Wilson, B. Ernst, S. J.C. Mancini, H. R. MacDonald, R. Kemler, and F. Radtke
{beta}-Catenin Is Dispensable for Hematopoiesis and Lymphopoiesis
J. Exp. Med., January 20, 2004; 199(2): 221 - 229.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
J. Yang, J. Wu, C. Tan, and P. S. Klein
PP2A:B56{epsilon} is required for Wnt/{beta}-catenin signaling during embryonic development
Development, December 1, 2003; 130(23): 5569 - 5578.
[Abstract] [Full Text] [PDF]

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 JCBHome page
A. Cattelino, S. Liebner, R. Gallini, A. Zanetti, G. Balconi, A. Corsi, P. Bianco, H. Wolburg, R. Moore, B. Oreda, et al.
The conditional inactivation of the {beta}-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility
J. Cell Biol., September 15, 2003; 162(6): 1111 - 1122.
[Abstract] [Full Text] [PDF]

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 Cereb CortexHome page
A. Chenn and C. A. Walsh
Increased Neuronal Production, Enlarged Forebrains and Cytoarchitectural Distortions in {beta}-Catenin Overexpressing Transgenic Mice
Cereb Cortex, June 1, 2003; 13(6): 599 - 606.
[Abstract] [Full Text] [PDF]

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 JCBHome page
M. G. Lampugnani, A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T. O. Daniel, et al.
Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, {beta}-catenin, and the phosphatase DEP-1/CD148
J. Cell Biol., May 26, 2003; 161(4): 793 - 804.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
I. Salazar-Ciudad, J. Jernvall, and S. A. Newman
Mechanisms of pattern formation in development and evolution
Development, May 15, 2003; 130(10): 2027 - 2037.
[Abstract] [Full Text] [PDF]

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 CROBMHome page
Y. Chai, Y. Ito, and J. Han
TGF-{beta} SIGNALING AND ITS FUNCTIONAL SIGNIFICANCE IN REGULATING THE FATE OF CRANIAL NEURAL CREST CELLS
Critical Reviews in Oral Biology & Medicine, March 1, 2003; 14(2): 78 - 88.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
J. R. Barrow, K. R. Thomas, O. Boussadia-Zahui, R. Moore, R. Kemler, M. R. Capecchi, and A. P. McMahon
Ectodermal Wnt3/beta -catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge
Genes & Dev., February 1, 2003; 17(3): 394 - 409.
[Abstract] [Full Text] [PDF]

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 JCBHome page
L. Hari, V. Brault, M. Kleber, H.-Y. Lee, F. Ille, R. Leimeroth, C. Paratore, U. Suter, R. Kemler, and L. Sommer
Lineage-specific requirements of {beta}-catenin in neural crest development
J. Cell Biol., December 9, 2002; 159(5): 867 - 880.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
B. Wortman, N. Darbinian, B. E. Sawaya, K. Khalili, and S. Amini
Evidence for Regulation of Long Terminal Repeat Transcription by Wnt Transcription Factor TCF-4 in Human Astrocytic Cells
J. Virol., October 2, 2002; 76(21): 11159 - 11165.
[Abstract] [Full Text] [PDF]

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 JCBHome page
H. R. Widlund, M. A. Horstmann, E. R. Price, J. Cui, S. L. Lessnick, M. Wu, X. He, and D. E. Fisher
{beta}-Catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor
J. Cell Biol., September 16, 2002; 158(6): 1079 - 1087.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
A. Chenn and C. A. Walsh
Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors
Science, July 19, 2002; 297(5580): 365 - 369.
[Abstract] [Full Text] [PDF]


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