Carol Marchetto, from the Salk Institute of Biological Studies, extended her previous characterization of a monogenic form of ASD (Rett syndrome) (Marchetto et al., 2010) by recruiting a genetically heterogeneous cohort of patients with ASD, characterized by an endophenotype of transient macrocephaly, and comparing them to gender- and age-matched unrelated controls. ASD-derived neural progenitor cells (NPCs) display increased cell proliferation due to a dysregulation of a β-catenin/BRN2 transcriptional cascade, while ASD-derived neurons displayed premature differentiation, reduced synaptogenesis, and altered levels of excitatory and inhibitory neurotransmitters, leading to functional defects in neuronal networks, measured by multielectrode arrays. Interestingly, RNA analysis also revealed increased expression of FOXG1 in ASD NPCs, in agreement with Flora Vaccarino’s data in a completely independent set of experiments, suggesting that there may be common features in macrocephalic ASD and pointing to a potential target of therapeutic intervention.
