Background <p>Parental experience can influence progeny behavior through gamete-mediated non-genetic inheritance, that is, mechanisms that do not involve changes in inherited DNA sequence. However, underlying mechanisms remain poorly understood in vertebrates, especially for maternal effects. Here, we use the medaka, a model fish species, to investigate the role of <i>auts2a</i>, the ortholog of human <i>AUTS2</i>, a gene repressed in the fish oocyte following maternal stress and associated with neurodevelopmental disorders.</p> Results <p>We show that <i>auts2a</i> expression in the oocyte influences long-term progeny behavior, including anxiety-like behavior and environment recognition capabilities. Using single-nuclei RNA-sequencing, we reveal that maternal <i>auts2a</i> influences gene expression in neural cell populations during neurodevelopment. We also show that maternal <i>auts2a</i> knock-out triggers differences in maternally inherited factors, including early embryonic transcriptional and post-transcriptional regulators.</p> Conclusions <p>Together, our results reveal the unsuspected role of an autism-related gene expressed in the mother’s oocyte in shaping progeny neurodevelopment and behavior. Finally, we report that <i>auts2a/AUTS2</i> is part of a group of evolutionarily conserved genes associated with human neurodevelopmental disorders and expressed in oocytes across species, from fish to mammals. These findings raise important questions about their potential role in the non-genetic regulation of progeny neurodevelopment and behavior in vertebrates.</p>

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Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish

  • Antoine Emile Clément,
  • Constance Merdrignac,
  • Sergi Roig Puiggros,
  • Dorine Sévère,
  • Aurélien Brionne,
  • Thomas Lafond,
  • Thaovi Nguyen,
  • Jérôme Montfort,
  • Cervin Guyomar,
  • Alexandra Dauvé,
  • Amaury Herpin,
  • Denis Jabaudon,
  • Violaine Colson,
  • Florent Murat,
  • Julien Bobe

摘要

Background

Parental experience can influence progeny behavior through gamete-mediated non-genetic inheritance, that is, mechanisms that do not involve changes in inherited DNA sequence. However, underlying mechanisms remain poorly understood in vertebrates, especially for maternal effects. Here, we use the medaka, a model fish species, to investigate the role of auts2a, the ortholog of human AUTS2, a gene repressed in the fish oocyte following maternal stress and associated with neurodevelopmental disorders.

Results

We show that auts2a expression in the oocyte influences long-term progeny behavior, including anxiety-like behavior and environment recognition capabilities. Using single-nuclei RNA-sequencing, we reveal that maternal auts2a influences gene expression in neural cell populations during neurodevelopment. We also show that maternal auts2a knock-out triggers differences in maternally inherited factors, including early embryonic transcriptional and post-transcriptional regulators.

Conclusions

Together, our results reveal the unsuspected role of an autism-related gene expressed in the mother’s oocyte in shaping progeny neurodevelopment and behavior. Finally, we report that auts2a/AUTS2 is part of a group of evolutionarily conserved genes associated with human neurodevelopmental disorders and expressed in oocytes across species, from fish to mammals. These findings raise important questions about their potential role in the non-genetic regulation of progeny neurodevelopment and behavior in vertebrates.