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PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice

ABSTRACT: Mammalian brain evolved through several transitions between gyrencephaly and lissencephaly. Mechanisms generating gyrified or smooth brain are incompletely understood. Here we demonstrate that a short embryonic pulse of activating mutations in Pik3ca, the catalytic subunit of PI3K enzyme is sufficient to cause mouse cortical gyrification. We demonstrate that this gyrification phenotype is initiated by subtle focal regulation of apical cell adhesion and proliferation via PI3K-dependent localization of Yap protein. Treatment with verteporfin (Drug) a nuclear Yap inhibitor, attenuated over-proliferation and adhesion abnormalities, and subsequently gyrification. The purpose of this study was to compare the control and mutant mouse transcriptome, and their respective effect upon verteprofin treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE127896 | GEO | 2019/05/15

REPOSITORIES: GEO

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PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice

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