Transcriptome of fetal cortex of tree shrew underlying the emergence of outer subventricular zone

Abstract A defining feature of primates is the expansion and increased complexity of the cerebral cortex, processes that are largely associated with evolutionary adaptations of the neural progenitor-enriched outer subventricular zone (OSVZ). Yet, the genetic mechanisms underlying the emergence of the primate OSVZ remain unknown. The tree shrew is a closer outgroup to primates than rodents, its brain exhibits an intermediate phenotype; while being lissencephalic , it nonetheless possesses an OSVZ. Here, we applied laser microdissection technology to conduct comprehensive gene expression analyses of different cortical layers in the tree shrew brain across three key developmental stages. We show that cell cycle-related genes are already involved in the tree shrew OSVZ. In contrast, extracellular matrix-associated pathways appear to be unique to the primate OSVZ. Furthermore, overexpression of ZNF664 significantly increased intermediate progenitor proliferation in the mouse subventricular zone. Together, these results reveal shared molecular mechanisms underlying OSVZ development in primates and tree shrews, providing insights into the origin of primate cortical complexity.