This study presents a single-nucleus multiomic atlas of the adult primate cerebellum, comparing humans with chimpanzees, macaques, and marmosets to identify species-specific evolutionary features. While most cerebellar cell types are conserved across primates, researchers discovered that human granule cells exhibit significant transcriptomic divergence, particularly in genes related to synaptogenesis and synaptic maturation. A key finding is the human-specific expression of ZP2, a protein typically associated with reproductive fertilization, which has been repurposed in the brain to regulate pontocerebellar glomerular synapses. Experimental data show that ZP2 acts as a feedback mechanism induced by pontine mossy fibers to restrict synapse formation and reduce neuronal activity during development. This molecular adaptation may explain the neotenic maturation and increased complexity of the human cerebellum compared to other primates. Additionally, the study links these evolutionary genetic changes to various neuropsychiatric and neurodegenerative disorders, providing a resource for understanding human brain dysfunction.

References:

• Kim S K, Cherskov A, Sindhwani A, et al. Human-specific features of the cerebellum and ZP2-regulated synapse development[J]. bioRxiv, 2025.