Species-specific basal fluidization shapes early forebrain development

The human forebrain exhibits an expanded surface area compared with other great apes. Despite rapid progress in dissecting species-specific gene expression programs and cell lineages, the tissue-level physical mechanisms underlying human-specific neurodevelopment remain unclear. By quantitatively characterizing tissue dynamics and mechanics with oil microdroplets in cerebral organoids derived from humans, gorillas, and mice, here we uncover a transient fluidization that occurs exclusively in the basal region of human neuroepithelia. Enhanced droplet motility and frequent cell rearrangements reveal this basal tissue fluidization, which is absent in gorilla and mouse neuroepithelia and diminishes in humans at the onset of neurogenesis. Basal fluidization is driven by nuclear movement fluctuations and facilitated by expanded intercellular spaces. Increasing N-cadherin expression in human neuroepithelia to gorilla levels suppresses both nuclear fluctuations and basal fluidity. Our findings identify transient basal fluidization as a novel mechanical hallmark of early human forebrain development, which may contribute to the tangential surface expansion unique to humans.