Linking ASD risk genes to sensorimotor circuits for dynamic social communication

Autism can occur in isolation or as part of a syndrome which includes other neurodevelopmental disorders. Mutations in genes that cause neurodevelopmental disorders and syndromic autism can have overlapping phenotypes indicating that the molecular pathways regulated by these genes may interact.

For example, Coffin-Siris syndrome 1, Pitt-Hopkins syndrome and syndromes associated with nuclear factor one (NFI) genes have overlapping neurological phenotypes including autism, intellectual disability and corpus callosum dysgenesis. Several lines of evidence suggest that the downstream pathways of causal genes for these disorders, ARID1B, TCF4 and NFI genes, respectively, may interact.

The Richards laboratory has been interrogating the function of the NFI genes and their involvement in brain development. There are four NFI genes in humans and mice: NFIA, NFIB, NFIC, and NFIX, but only three (A, B and X) are expressed in brain. In this project the Richards lab is using mouse models for ARID1B, TCF4 and NFI to investigate whether they function at the same regions of the chromatin and if they regulate similar cellular and molecular processes in radial glial populations of the cerebral cortex.

By identifying key cellular and molecular pathways that could underlie the overlapping phenotypes observed in these neurodevelopmental disorders, this work has significant implications for understanding whether these disorders share common underlying etiologies.