APC sets the Wnt tone necessary for cerebral cortical progenitor development

Genes Dev. 2017 Aug 15;31(16):1679-1692. doi: 10.1101/gad.302679.117. Epub 2017 Sep 15.


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

Keywords: APC; Wnt signaling; autism; cerebral cortical development; cortical progenitors; primary cilia; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / physiology*
  • Animals
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Cilia / metabolism
  • Hedgehog Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis*
  • Receptor, Notch1 / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / physiology


  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, mouse
  • Hedgehog Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Shh protein, mouse
  • adenomatous polyposis coli protein, mouse
  • beta Catenin