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| Status |
Public on May 15, 2019 |
| Title |
PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
Mouse RNA profiles from postnatal day (P)0 hGFAP-cre;Pik3ca H1047R mutant and control hippocampal CA1 region, in presence or absence of a drug Verteporfin
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| Contributor(s) |
Roy A, Aldinger KA, Millen KJ |
| Citation(s) |
31094678 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 NS099027 |
Mouse models of Pik3ca brain overgrowth disorders |
SEATTLE CHILDREN'S RESEARCH INSTITUTE |
Kathleen Joyce Millen |
| U54 HD083091 |
Intellectual and Developmental Disabilities Research Center |
UNIVERSITY OF WASHINGTON |
Michael J Guralnick |
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| |
| Submission date |
Mar 05, 2019 |
| Last update date |
May 17, 2019 |
| Contact name |
Kimberly A Aldinger |
| E-mail(s) |
kimberly.aldinger@seattlechildrens.org
|
| Organization name |
Seattle Children's Research Institute
|
| Street address |
1900 Nineth Ave
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98101 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA525718 |
| SRA |
SRP187615 |
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