APC sets the Wnt tone necessary for cerebral cortical progenitor development.
Genes Dev
; 31(16): 1679-1692, 2017 08 15.
Article
em En
| MEDLINE
| ID: mdl-28916710
ABSTRACT
Adenomatous polyposis coli (APC) regulates the activity of ß-catenin, an integral component of Wnt signaling. However, the selective role of the APC-ß-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated ß-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-ß-catenin pathway indicates that the maintenance of appropriate ß-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates ß-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. ß-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of ß-catenin or inhibition of ß-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated ß-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
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Proteína da Polipose Adenomatosa do Colo
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Neurogênese
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Células-Tronco Neurais
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Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article