BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.

Zhenmeiyu LI; Guoping Liu; Lin Yang; Mengge Sun; Zhuangzhi Zhang; Zhejun XU; Yanjing Gao; Xin Jiang; Zihao SU; Xiaosu LI; Zhengang Yang

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BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.

Author: Zhenmeiyu LI ¹ ; Guoping LIU ¹ ; Lin YANG ¹ ; Mengge SUN ¹ ; Zhuangzhi ZHANG ¹ ; Zhejun XU ¹ ; Yanjing GAO ¹ ; Xin JIANG ¹ ; Zihao SU ¹ ; Xiaosu LI ¹ ; Zhengang YANG ¹
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1. State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, and Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
Publication Type:Journal Article
Keywords: BMP7; SHH; cortical evolution; cortical gliogenesis; cortical neurogenesis; radial glia
MeSH: Animals; Mice; Humans; Ependymoglial Cells/metabolism*; Hedgehog Proteins/metabolism*; Ferrets/metabolism*; Cerebral Cortex; Neurogenesis; Mammals/metabolism*; Neuroglia/metabolism*; Bone Morphogenetic Protein 7/metabolism*
From: Protein & Cell 2024;15(1):21-35
CountryChina
Language:English
Abstract: The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.