Date of Award

2017

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Maldonado, Monica

Abstract

Heterozygous mutations in PTEN are known to cause features of head overgrowth (macrocephaly) and autism spectrum disorder (ASD). PTEN is a lipid phosphatase that functions as a negative regulator of the PI3K-AKT-mTOR cell signaling pathway, which is crucial to cell growth and proliferation. In this study, we utilized a transgenic mouse model of macrocephaly/autism syndrome (Pten haploinsufficient mice) to generate cultures of primary neurons that display structural defects (e.g. neurite overgrowth and cell soma size) as compared to neurons derived from wild-type animals. We hypothesize that restoration of Pten levels in neurons derived from Pten haploinsufficient mice will restore normal functioning of the PI3K-AKT-mTOR signaling pathway, which in turn will reverse the morphological abnormalities seen in these cells. Our results indicate that adding a cell penetrating isoform of PTEN to haploinsufficient primary cortical neurons resulted in a rescue of the increased primary branching that is seen in Pten haploinsufficient cultures.

Comments

Includes bibliography.

Extent

32 p.

Identifier

FA00012647

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