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Neocortex expansion and folding are related to human intelligence and cognition, but the molecular and cellular mechanisms underlying cortical folding remain poorly understood. Here, we report that the human gene SERPINA3 is linked to gyrification. Specifically, the overexpression of SERPINA3 induced neocortical folding, increased the abundance of neurons, and improved cognitive abilities. Further, SERPINA3 promoted proliferation of the outer radial glia (oRG, also referred to as the basal radial glia) and increased the number of upper-layer neurons. The downstream target Glo1 was determined to be involved in SERPINA3-induced gyrification. Moreover, SERPINA3 increased the proliferation of oRG by binding to the Glo1 promoter. Assessment of behavior performance showed enhanced cognitive abilities in SERPINA3 knock-in mice. Our findings will enrich the understanding of neocortical expansion and gyrification and provide insights into possible treatments for intellectual disability and lissencephaly syndrome.
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http://dx.doi.org/10.1038/s41421-022-00469-0 | DOI Listing |
Neuroscience
June 2025
Jing'an District Central Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address:
Neocortical folding (i.e., gyrification) is a key evolutionary and developmental feature of the brain, facilitating cortical surface expansion and enhanced cognitive function.
View Article and Find Full Text PDFCurr Opin Genet Dev
December 2024
German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany. Electronic address:
The evolutionary expansion of the neocortex in the ape lineage is the basis for the development of higher cognitive abilities. However, the human brain has uniquely increased in size and degree of folding, forming an essential foundation for advanced cognitive functions. This raises the question: what factors distinguish humans from our closest living primate relatives, such as chimpanzees and bonobos, which exhibit comparatively constrained cognitive capabilities? In this review, we focus on recent studies examining (modern) human-specific genetic traits that influence neural progenitor cells, whose behavior and activity are crucial for shaping cortical morphology.
View Article and Find Full Text PDFNeurosci Bull
March 2025
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Neurology, Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Human's robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes made to the cerebral cortex. This paper reviews the biology and evolution of mammalian cortical radial glial cells (primary neural stem cells) and introduces the concept that a genetically step wise process, based on a core molecular pathway already in use, is the evolutionary process that has molded cortical neurogenesis. The core mechanism, which has been identified in our recent studies, is the extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop.
View Article and Find Full Text PDFJ Comp Neurol
June 2024
Centro de Estudios Biomédicos Básicos, Aplicados y Desarrollo (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina.
Commun Biol
May 2024
Department of Sport Science, Institute III, Faculty of Humanities, Otto von Guericke University, Zschokkestraße 32, 39104, Magdeburg, Germany.
The capacity to learn enabled the human species to adapt to various challenging environmental conditions and pass important achievements on to the next generation. A growing body of research suggests links between neocortical folding properties and numerous aspects of human behavior, but their impact on enhanced human learning capacity remains unexplored. Here we leverage three training cohorts to demonstrate that higher levels of premotor cortical folding reliably predict individual long-term learning gains in a challenging new motor task, above and beyond initial performance differences.
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