Human SERPINA3 induces neocortical folding and improves cognitive ability in mice
Abstract 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 SERPIN...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-11-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-022-00469-0 |
| _version_ | 1797986707982778368 |
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| author | Jinyue Zhao Chao Feng Wenwen Wang Libo Su Jianwei Jiao |
| author_facet | Jinyue Zhao Chao Feng Wenwen Wang Libo Su Jianwei Jiao |
| author_sort | Jinyue Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T07:36:20Z |
| format | Article |
| id | doaj.art-51fcb0dfb65a4abd8631d228c0d1f4d4 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-11T07:36:20Z |
| publishDate | 2022-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-51fcb0dfb65a4abd8631d228c0d1f4d42022-12-22T04:36:43ZengNature Publishing GroupCell Discovery2056-59682022-11-018111910.1038/s41421-022-00469-0Human SERPINA3 induces neocortical folding and improves cognitive ability in miceJinyue Zhao0Chao Feng1Wenwen Wang2Libo Su3Jianwei Jiao4State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41421-022-00469-0 |
| spellingShingle | Jinyue Zhao Chao Feng Wenwen Wang Libo Su Jianwei Jiao Human SERPINA3 induces neocortical folding and improves cognitive ability in mice Cell Discovery |
| title | Human SERPINA3 induces neocortical folding and improves cognitive ability in mice |
| title_full | Human SERPINA3 induces neocortical folding and improves cognitive ability in mice |
| title_fullStr | Human SERPINA3 induces neocortical folding and improves cognitive ability in mice |
| title_full_unstemmed | Human SERPINA3 induces neocortical folding and improves cognitive ability in mice |
| title_short | Human SERPINA3 induces neocortical folding and improves cognitive ability in mice |
| title_sort | human serpina3 induces neocortical folding and improves cognitive ability in mice |
| url | https://doi.org/10.1038/s41421-022-00469-0 |
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