Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden School of Medicine, 013107 Dresden, Germany.
Cells. 2023 Oct 3;12(19):2400. doi: 10.3390/cells12192400.
The localization, expression, and physiological role of regulatory proteins in the neurogenic niches of the brain is fundamental to our understanding of adult neurogenesis. This study explores the expression and role of the E3-ubiquitin ligase, c-Cbl, in neurogenesis within the subventricular zone (SVZ) of mice. In vitro neurosphere assays and analyses were performed in specific c-Cbl knock-out lines to unravel c-Cbl's role in receptor tyrosine kinase signaling, including the epidermal growth factor receptor (EGFR) pathway. Our findings suggest that c-Cbl is significantly expressed within EGFR-expressing cells, playing a pivotal role in neural stem cell proliferation and differentiation. However, c-Cbl's function extends beyond EGFR signaling, as its loss upon knock-out stimulated progenitor cell proliferation in neurosphere cultures. Yet, this effect was not detected in hippocampal progenitor cells, reflecting the lack of the EGFR in the hippocampus. , c-Cbl exerted only a minor proneurogenic influence with no measurable impact on the formation of adult-born neurons. In conclusion, c-Cbl regulates neural stem cells in the subventricular zone via the EGFR pathway but, likely, its loss is compensated by other signaling modules .
调节蛋白在脑的神经发生龛中的定位、表达和生理作用，是我们理解成年神经发生的基础。本研究探讨了 E3 泛素连接酶 c-Cbl 在小鼠侧脑室下区（SVZ）神经发生中的表达和作用。在特定的 c-Cbl 敲除系中进行体外神经球测定和分析，以揭示 c-Cbl 在受体酪氨酸激酶信号转导中的作用，包括表皮生长因子受体（EGFR）途径。我们的研究结果表明，c-Cbl 在表达 EGFR 的细胞中显著表达，在神经干细胞的增殖和分化中发挥关键作用。然而，c-Cbl 的功能超出了 EGFR 信号，因为其敲除后在神经球培养物中刺激祖细胞增殖。然而，在海马祖细胞中未检测到这种效应，这反映了海马中缺乏 EGFR。总之，c-Cbl 通过 EGFR 途径调节侧脑室下区的神经干细胞，但可能通过其他信号模块的缺失来代偿其缺失。
