Reintroduction of the archaic variant of <i>NOVA1</i> in cortical organoids alters neurodevelopment
Cleber A. Trujillo, Edward S. Rice, Nathan K. Schaefer, Isaac A. Chaim, Emily C. Wheeler, Assael A. Madrigal, Justin Buchanan, Sebastian Preißl, Allen Wang, Priscilla D. Negraes, Ryan A. Szeto, Roberto H. Herai, Alik Huseynov, Mariana Sacrini Ayres Ferraz, Fernando S. Borges, Alexandre Hiroaki Kihara, Ashley Byrne, Maximillian G. Marin, Christopher Vollmers, Angela N. Brooks, Jonathan D. Lautz, Katerina Semendeferi, Beth Shapiro, G Yeo, Stephen Smith, Richard E. Green, Alysson R. Muotri
Abstract
Brain organoids with Neanderthal genes The genomes of Neanderthals and modern humans are overall very similar. To understand the impact of genetic variants that are specific to modern humans, Trujillo et al. performed a genome-wide analysis to identify 61 coding variants in protein-coding genes. Identifying the gene encoding the RNA-binding protein NOVA1 as a top candidate for functional analyses, they introduced the archaic gene variant into human pluripotent stem cells and generated brain organoids. These organoids showed alterations in gene expression and splicing as well as morphology and synaptogenesis, suggesting that this method could be used to explore other genetic changes that underlie the phenotypic traits separating our species from extinct relatives. Science , this issue p. eaax2537