β‐catenin–mediated cell‐adhesion is vital for embryonic forebrain development

Abstract

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. Developmental Dynamics 233:528–539, 2005. © 2005 Wiley‐Liss, Inc.