Regulation of sociality and neuronal development by the translation initiation factor eIF4H1 in Drosophila

Most animal species exhibit some level of sociality. However, whether sociality-related traits evolved independently, or are instead derived from common core mechanisms, remains controversial. Nevertheless, an emerging theoretical framework stipulates that key aspects of how animals interact with their social environments may be regulated by a phylogenetically conserved genetic toolkit. Therefore, we hypothesized that mutations that lead to social deficits in specific human disorders may implicate genes that play conserved roles in the regulation of core social traits across Animalia. Specifically, here we focus on genes associated with Williams syndrome (WS), a rare human multi-system disorder characterized in part by hypersocial cognitive traits. WS is caused by a hemizygous chromosomal microdeletion of 25-28 protein-coding genes. Consequently, it has been hypothesized that haploinsufficiency in at least one of these genes plays an important role in the development and/or function of social neural circuits in humans. Because the Drosophila genome encodes orthologs of 17 of the 28 genes deleted in WS, we reasoned that at least some of them may serve a conserved role in the regulation of social traits across flies and humans, as predicted by the genetic toolkit framework. Using a neuron-specific RNAi knockdown screen, we identified eIF4H1, an ortholog of a highly conserved subunit of the eukaryotic translation initiation complex eIF4F, as a candidate gene for neuronal regulation of sociality in the fly. We show that eIF4H1 expression is predominantly neuronal in the adult fly brain, and that its action plays a differential role in the organization of specific dopaminergic neuron subtypes that are associated with sociality and cognitive functions. These results indicate that eIF4H1 may serve a conserved function in regulating the development of the neuronal circuits that regulate social behaviors, thus supporting the idea of a conserved sociality genetic toolkit.