Mechanisms underlying genetic and environmental associations with autism

Abstract

Both genetic variants and environmental exposures have been identified that increase the likelihood of being diagnosed with autism. However, the molecular, cellular, and systems level cascade by which genetic factors, or their interaction with environment, lead to an autism diagnosis is largely unknown. In this talk, I will first present work from our lab describing the impact of autism associated mutations in the gene Chd8 on brain structure using a mouse model. Using tissue clearing and lightsheet microscopy, we explain the cellular basis underlying macrocephaly observed in this model, and we also discover and replicate molecular layer heterotopias, where neurons overmigrate beyond the pial border. Next, moving to a human model system, I will present our work developing human cortical organoid models from the densely phenotyped Infant Brain Imaging Study, allowing assessment of the in vivo fidelity of brain organoids for measuring differences in brain size. Finally, I will present our work evaluating molecular gene by environment interactions in a dish, a well-controlled alternative approach to epidemiological studies that are subjected to confounding effects. We find that genetic variants modulate response to valproic acid, a known autism environmental risk factor, in this developing cell type. In all, our work aims to better explain the mechanisms by which genetic variants, and their interaction with environment, alters brain development.

Join us on Monday, August 24 at 1:30 PM in Stephens Room (3503 Thomas Hall) and ZOOM for the Genetics and Genomics Seminar Series. This event will be held in person in Stephens Room (3503 Thomas Hall) and on Zoom.

Attend via Zoom:

Please contact host Jennifer Ocasio Adorno ([email protected]) with any questions.