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β-catenin, forebrain, cell-adhesion, N-cadherin, FoxG1-Cre, apoptosis
Abstract:
Forming a complex structure such as the mammalian brain requires a complex interplay between cells and different signalling cascades during embryonic development. β-catenin plays pivotal roles in these processes by mediating cadherin-based cell adhesion and Wnt signalling. We show for the first time that β-catenin functions predominantly as a mediator of cell adhesion during early development of the mammalian telencephalon. Immunohistochemical analysis demonstrates that β-catenin is localized, together with N-cadherin, to adhesion junctions at the apical lining of the neuroepithelium. The ablation of β-catenin specifically from the forebrain leads to a disruption of apical adherens junctions and a breakdown of neuroepithelial structures. We show that β-catenin-deficient neuroepithelial cells delaminate and undergo apoptosis. Newborn β-catenin mutants lack the entire forebrain and anterior facial structures. Our data also indicate a lack of TCF/LEF-β-catenin-dependent transcriptional activity in the telencephalon of Wnt reporter embryos. Together with the absence of nuclear β-catenin, this finding suggests that canonical Wnt signalling is not active during early telencephalic development. In summary, we demonstrate that β-catenin mediates cell-cell adhesion in the early telencephalon and is vital for maintaining the structural integrity of the neuroepithelium.
