APC sets the Wnt tone necessary for cerebral cortical progenitor development.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Nakagawa N,Li J,Yabuno-Nakagawa K,Eom TY,Cowles M,Mapp T,Taylor R,Anton ES

doi

10.1101/gad.302679.117

subject

Has Abstract

pub_date

2017-08-15 00:00:00

pages

1679-1692

issue

16

eissn

0890-9369

issn

1549-5477

pii

gad.302679.117

journal_volume

31

pub_type

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