Autism spectrum disorder (ASD) is characterized by deficits in social interaction and language as well as ritualistic behaviors. There is rapid progress in identifying large numbers of candidate ASD alleles. A rate limiting step in demonstrating the biological relevance of these alleles are assays that discern whether they alter neuronal development and/or function. This project describes a novel assay to test whether ASD mutant alleles alter the development of mouse cortical interneurons. It focuses on the effect of these alleles on cortical interneurons, because this cell type is implicated in ASD (based in part on high rates of epilepsy), and because they are particularly amenable to experimental analysis based on their ability to be transplanted efficiently into the postnatal cortex. For a proof of principle of this approach, the experiments will study the function of ASD alleles of PTEN, a phosphatase gene that is implicated in ASD with macrocephaly. This study has two Aims: 1) Examine in vivo phenotypes of transplanted PTEN-/- interneurons and 2) Functional assessment of ASD PTEN mutant alleles using interneuron transplantation. Aim 1 assesses PTEN’s function in cortical interneuron development, as this cell type has recently been shown to be important for behavioral phenotypes in an ASD mouse model (Mecp2 mutants). The investigators use the medial ganglionic eminence (MGE) transplantation assay to study the development of PTEN-/- cortical interneurons. Following transplantation, their molecular and cellular maturation will be monitored. Aim 2 assesses the function of ASD PTEN mutant alleles using the MGE transplantation assay. The ability of WT and ASD PTEN mutant alleles for their ability to rescue development of interneurons in vivo, derived from PTEN-/- MGE. It is hypothesized that the MGE transplantation assay can be easily modified for future studies to assess the function of alleles from other ASD candidate genes.