University of California Television (UCTV)

CARTA: Neanderthalizing Brain Organoids with Alysson Muotri

Humans live in a world of ideas—born in the brain, shared through language, accumulated in culture across generations, and made reality. Professor Alysson Muotri, UC San Diego Departments of Pediatrics and Cellular and Molecular Medicine, examines how human brain evolution reflects the interplay between genetic innovation and environmental pressures, focusing on Neuro-oncological ventral antigen 1 (NOVA1), an evolutionarily conserved splicing regulator essential for neural development with a protein-coding substitution unique to modern humans compared with Neanderthals and Denisovans. By reintroducing the archaic NOVA1 allele into human induced pluripotent stem cells and studying cortical organoids, the work finds accelerated maturation, increased surface complexity, altered synaptic marker expression, and changes in electrophysiological properties. Muotri also analyzes long-term lead exposure using fossilized teeth from multiple hominid species spanning over two million years, revealing pervasive exposure across extinct and extant hominids. Lead exposure selectively disrupted FOXP2 expression in cortical and thalamic organoids carrying the archaic NOVA1 variant, and findings were independently validated in NOVA1 humanized mouse models with altered vocalization. Together, these results suggest gene–environment interactions may have influenced neural circuit development, social behavior, and complex language capacity. Recorded on 02/27/2026. [3/2026] [Show ID: 41297] Donate to UCTV to support informative & inspiring programming: https://www.uctv.tv/donate Learn more about anthropogeny on CARTA's website: https://carta.anthropogeny.org/ Explore More Science & Technology on UCTV (https://www.uctv.tv/science) Science and technology continue to change our lives. University of California scientists are tackling the important questions like climate change, evolution, oceanography, neuroscience and the potential of stem cells. UCTV is the broadcast and online media platform of the University of California, featuring programming from its ten campuses, three national labs and affiliated research institutions. UCTV explores a broad spectrum of subjects for a general audience, including science, health and medicine, public affairs, humanities, arts and music, business, education, and agriculture. Launched in January 2000, UCTV embraces the core missions of the University of California -- teaching, research, and public service – by providing quality, in-depth television far beyond the campus borders to inquisitive viewers around the world. (https://www.uctv.tv)