APC sets the Wnt tone necessary for cerebral cortical progenitor development

作者：Nakagawa Naoki; Li Jingjun; Yabuno Nakagawa Keiko; Eom Tae Yeon; Cowles Martis; Mapp Tavien; Taylor Robin; Anton E S^*

来源：Genes & Development, 2017, 31(16): 1679-1692.

DOI：10.1101/gad.302679.117

• cortical progenitors
• APC
• beta-catenin
• cerebral cortical development
• Wnt signaling
• primary cilia
• autism

Adenomatous polyposis coli (APC) regulates the activity of beta-catenin, an integral component of Wnt signaling. However, the selective role of the APC-beta-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated beta-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-beta-catenin pathway indicates that the maintenance of appropriate beta-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates beta-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. beta-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of beta-catenin or inhibition of beta-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated beta-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development.

• 出版日期2017-8-15