Genetic Dissection of Steroid-hormone Modulated Social Behavior: Novel Paralogous Genes Are a Boon for Discovery

Research across species has led to important discoveries on the functions of steroid hormones in the regulation of behavior. However, like in many fields, advancements in transgenic and mutagenic technology allowed mice to become the premier genetic model for conducting many experiments to understand how steroids control social behavior. Since there has been a general lack of parallel methodological developments in other species, many of the findings cannot be generalized. This is especially the case for teleost fish, in which a whole-genome duplication produced novel paralogs for key steroid hormone signaling genes. In this review, we summarize technical advancements over the history of the field of neuroendocrinology that have led to important insights in our understanding of the control of social behavior by steroids. We demonstrate that early mouse genetic models to understand these mechanisms suffered from several issues that were remedied by more precise transgenic technological advancements. We then highlight the importance of CRISPR/Cas9 gene editing tools that will in time bridge the gap between mice and non-traditional model species for understanding principles of steroid hormone action in the modulation of social behavior. We specifically highlight the role of teleost fish in bridging this gap because they are 1) highly genetically tractable and 2) provide a novel advantage in achieving precise genetic control. The field of neuroendocrinology is entering a new "gene editing revolution" that will lead to novel discoveries about the roles of steroid hormones in the regulation and evolutionary trajectories of social behavior.