Species-Specific Parent-Of-Origin Expression of Adam23 in the Mammalian Brain

Genomic imprinting is a parent-of-origin-dependent epigenetic mechanism with established roles in placental development and fetal growth in mice, whereas its contribution to brain function and evolution remains incompletely understood. Here, we investigated parent-of-origin-biased gene expression in the ferret, a gyrencephalic mammal whose cortical architecture more closely resembles that of humans than mice. Guided by human imprinting datasets, we screened 65 candidate genes in the ferret brain and identified paternal allele-biased expression of Adam23, maternal bias of Atp10a, and biallelic expression of genes including Pxdc1, Wrb, and Ube3a. Adam23 showed paternal bias in the ferret cortex, most prominently in the occipital region, whereas it was biallelically expressed in mouse brain. In human SH-SY5Y cells, ADAM23 was biallelically expressed in undifferentiated cells but shifted toward allele-specific bias upon neuronal differentiation. Analysis of CpG islands upstream of Adam23 revealed no detectable promoter methylation, suggesting that canonical promoter methylation does not underlie this bias. Functional perturbation in Neuro-2aTG cells showed that reduced Adam23 expression enhanced neurite outgrowth, whereas increased dosage promoted cell proliferation. Together, these findings identify Adam23 as a gene with species- and context-dependent parent-of-origin expression bias and dosage-sensitive cellular effects, linking imprinting-related regulation to neural developmental processes in gyrencephalic brains.