Circuit mechanisms of 16p11.2 deletion in autism

Deletion of the 500KB 16p11.2 region has been discovered as a major risk factor for autism spectrum disorder. Our laboratory is part of a targeted project of the Simons Center for the Social Brain aimed at a multi-level analysis of the effects and mechanisms of 16p11.2 deletion. Major vault protein (MVP) is one of the genes within a 118Kb subset of the 16p11.2 region that likely has a crucial role in specific phenotypes of 16p11.2 deletion. In vitro, MVP is known to regulate intracellular signaling cascades including PI3K/Akt, MAPK and JAK/STAT pathways, all of which are required for synaptic and cortical plasticity. These pathways, and in particular Ras signaling, have been implicated in autism pathophysiology. The goal of this project is to determine the function of MVP in synaptic and cortical plasticity.