Pten Mutations Alter Brain Growth Trajectory and Allocation of Cell Types through Elevated β-Catenin Signaling.

Abstract

We report that Pten haploinsufficiency leads to a dynamic trajectory of brain overgrowth during development and altered scaling of neuronal and glial cell populations. β-catenin signaling is elevated in the developing cerebral cortex of Pten haploinsufficient mice, and a heterozygous mutation in β-catenin, itself a candidate gene for ASD and microcephaly, suppresses Pten(+/-) cortical overgrowth. This leads to the new insight that Pten and β-catenin signaling act in a common pathway to regulate normal brain growth trajectory by controlling cell number, and disruption of this pathway can result in abnormal brain growth.