Deciphering autism spectrum disorder genomic variation through the characterization of zebrafish and human stem cell-based models

Resumo

Autism Spectrum Disorders are characterized by behavioural, social, and communication impairments. Despite their prevalence, the precise mechanisms underlying ASD are poorly understood. This thesis is focused on developing suitable models to study the impact of mutations in three genes (BTBD8, FOSL2, and TAOK1) potentially associated with ASD. In vitro models were generated using human iPSCs that were differentiated into cortical neurons and human brain organoids, that were characterized through proteomics and scRNA-seq. Genes of interest were also studied in Danio rerio, to evaluate the morphological and behavioural consequences of gene dysfunction. These models will be useful for improving our understanding of the molecular mechanisms underlying ASD, but also for improving the diagnosis and treatment of the disorder.