| First Author | Nakagawa N | Year | 2017 |
| Journal | Genes Dev | Volume | 31 |
| Issue | 16 | Pages | 1679-1692 |
| PubMed ID | 28916710 | Mgi Jnum | J:309437 |
| Mgi Id | MGI:6754526 | Doi | 10.1101/gad.302679.117 |
| Citation | Nakagawa N, et al. (2017) APC sets the Wnt tone necessary for cerebral cortical progenitor development. Genes Dev 31(16):1679-1692 |
| abstractText | 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. |
