PhD defense of Constance Merdrignac

Parental life history can shape progeny phenotype through mechanisms that do not involve changes in gamete DNA sequence. This work explores the involvement of the auts2a gene in this non-genetic inheritance and in the regulation of progeny neurodevelopment and behaviour. AUTS2 is involved in various human neuropathologies. Its features and expression, notably in the oocyte, are conserved between mammals and teleost. In medaka, maternal auts2a expression regulates progeny neurodevelopment and behaviour. More precisely, it regulates anxiety-like behaviour and learning capabilities. In individuals sharing the same genotype, neural cell transcriptome at an early stage of neurodevelopment is mediated by parental auts2a expression. In the oocyte, auts2a expression regulates maternal mRNAs levels responsible for early development of the embryo, before the expression of its own genes. This work is one of the few associating non-genetic oocyte modifications (here, differences in maternal mRNAs levels) mediated by the maternal expression of a single gene, to progeny long-term phenotypic variations. More generally, it questions the role of the oocyte expression of other neurodevelopmental genes in the control of progeny behaviour and the conservation of the underlying mechanisms.