Maternal auts2a contribution is a major intergenerational driver of neurodevelopment and behavior

Abstract

AUTS2 gene has been associated with numerous human pathologies including autism. The respective importance of its maternal and paternal contribution remains however unknown. Here we show using a vertebrate model that the lack of maternal, but not paternal, gene contribution triggers reduced embryonic survival and long-term macroscopic and behavioral differences, including reduced head size and reduced environment recognition abilities and anxiety. Maternal auts2 modulates maternally-inherited factors that control, in turn, early embryonic gene expression through transcriptional and post-transcriptional regulations, and ultimately regulate numerous transcription factors and evolutionarily conserved signaling pathways during neurodevelopment. We observed a significant enrichment in genes associated with human neuropathologies among genes that are under maternal auts2control. We report that AUTS2 belongs to a group of 45 evolutionarily-conserved maternally-expressed genes associated with behavior and neurodevelopment in vertebrates and linked to a diversity of human diseases. These results shed new light on intergenerational determinism of neurodevelopment and behavior in vertebrates, including in the context of human pathologies associated with AUTS2.