Yakovleva Sophia, Knyazeva Anastasia, Yunusova Anastasia, Allayarova Elina, Lanshakov Dmitriy, Malashicheva Anna, Shnaider Tatiana
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Department of Natural Sciences, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2025 Jul 29;26(15):7309. doi: 10.3390/ijms26157309.
The Notch signaling pathway is a critical regulator of embryonic brain development. Among its four mammalian receptors, Notch1 and Notch2 are particularly significant in the developing cortex, yet their roles in human neurodevelopment are not well understood. In murine cortex development, primarily regulates early progenitor identity and neurogenesis, while is required for maintaining radial glial cells at later stages. However, it is unclear whether these functions are conserved in the human developing brain. In this study, we used cerebral organoids as an in vitro model of early human corticogenesis and conducted lentiviral shRNA-mediated knockdowns of and . Our findings indicate that is essential for organoid growth, lumen morphogenesis, radial glial identity, and progenitor proliferation. In contrast, depleting did not significantly affect these early developmental processes. These results demonstrate that and have potentially non-redundant and temporally distinct roles in early human corticogenesis, reflecting receptor-specific specialization within the Notch signaling pathway.
Notch信号通路是胚胎脑发育的关键调节因子。在其四种哺乳动物受体中,Notch1和Notch2在发育中的皮层中尤为重要,但其在人类神经发育中的作用尚未得到充分了解。在小鼠皮层发育中,主要调节早期祖细胞的特性和神经发生,而在后期维持放射状胶质细胞则需要 。然而,尚不清楚这些功能在人类发育中的大脑中是否保守。在本研究中,我们使用脑类器官作为早期人类皮质发生的体外模型,并通过慢病毒shRNA介导对 和 进行敲低。我们的研究结果表明, 对于类器官生长、管腔形态发生、放射状胶质细胞特性和祖细胞增殖至关重要。相比之下,耗尽 并没有显著影响这些早期发育过程。这些结果表明, 和 在早期人类皮质发生中具有潜在的非冗余和时间上不同的作用,反映了Notch信号通路中受体特异性的特化。
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