Beta-catenin-mediated cell-adhesion is vital for embryonic forebrain development.
Forming a complex structure such as the mammalian brain requires a complex interplay between cells and different signalling cascades during embryonic development. beta-catenin plays pivotal roles in these processes by mediating cadherin-based cell adhesion and Wnt signalling. We show for the first time that beta-catenin functions predominantly as a mediator of cell adhesion during early development of the mammalian telencephalon. Immunohistochemical analysis demonstrates that beta-catenin is localized, together with N-cadherin, to adhesion junctions at the apical lining of the neuroepithelium. The ablation of beta-catenin specifically from the forebrain leads to a disruption of apical adherens junctions and a breakdown of neuroepithelial structures. We show that beta-catenin-deficient neuroepithelial cells delaminate and undergo apoptosis. Newborn beta-catenin mutants lack the entire forebrain and anterior facial structures. Our data also indicate a lack of TCF/LEF-beta-catenin-dependent transcriptional activity in the telencephalon of Wnt reporter embryos. Together with the absence of nuclear beta-catenin, this finding suggests that canonical Wnt signalling is not active during early telencephalic development. In summary, we demonstrate that beta-catenin mediates cell-cell adhesion in the early telencephalon and is vital for maintaining the structural integrity of the neuroepithelium.
Junghans
Dirk
D
Max-Planck Institute of Immunobiology, Department of Molecular Embryology, Freiburg, Germany.
Hack
Iris
I
Frotscher
Michael
M
Taylor
Verdon
V
Kemler
Rolf
R
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin