ERK signaling expands mammalian cortical radial glial cells and extends the neurogenic period

• 成果类型: Article
• 署名作者: Sun, Mengge; Gao, Yanjing; Li, Zhenmeiyu; Yang, Lin; Liu, Guoping; Xu, Zhejun; Guo, Rongliang; You, Yan; Yang, Zhengang
• 署名单位: Fudan University; Fudan University; Fudan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9558
• DOI: 10.1073/pnas.2314802121
• 发表日期: 2024-03-26
• 关键词: fibroblast growth-factors; rostral prosencephalon; multiple roles; neocortex; fgf8; regionalization; achondroplasia; proliferation; expression; EVOLUTION

摘要

The molecular basis for cortical expansion during evolution remains largely unknown. Here, we report that fibroblast growth factor (FGF)- extracellular signal- regulated kinase (ERK) signaling promotes the self-renewal and expansion of cortical radial glial (RG) cells. Furthermore, FGF-ERK signaling induces bone morphogenic protein 7 (Bmp7) expression in cortical RG cells, which increases the length of the neurogenic period. We demonstrate that ERK signaling and Sonic Hedgehog (SHH) signaling mutually inhibit each other in cortical RG cells. We provide evidence that ERK signaling is elevated in cortical RG cells during development and evolution. We propose that the expansion of the mammalian cortex, notably in human, is driven by the ERK- BMP7-GLI3R signaling pathway in cortical RG cells, which participates in a positive feedback loop through antagonizing SHH signaling. We also propose that the relatively short cortical neurogenic period in mice is partly due to mouse cortical RG cells receiving higher SHH signaling that antagonizes ERK signaling.