Convergent thyroid-ATPase interactions regulate collective behavior in Danionella

Collective behavior emerges from socially interacting individuals. Across species, the social behavior of healthy adults is often not present in immature animals, in socially isolated animals, or in animals with certain genetic perturbations, including models of autism spectrum disorder (ASD). Although social behavior is impaired in all these conditions, it remains unclear whether they act through shared or distinct genetic pathways. Here, we investigate the genetic regulators of collective schooling behavior in Danionella cerebrum, by applying RNA sequencing to the brains of animals with impaired or immature social behavior: juvenile animals, socially isolated adults, and ASD-related gene crispants. By comparing gene expression to controls, we identify a small set of differentially expressed genes common to these conditions, including thyroid signaling pathway, circadian rhythm-regulating genes, the transcription factor klf9, and the ATPase subunit atp1a1a.4. Genetic and pharmacological manipulations confirm their functional importance, demonstrating convergent molecular pathways regulating social interactions and collective behavior.