Research output: Contribution to journal › Article › peer-review
Functional Divergence of NOTCH1 and NOTCH2 in Human Cerebral Organoids Reveals Receptor-Specific Roles in Early Corticogenesis. / Yakovleva, Sophia; Knyazeva, Anastasia; Yunusova, Anastasia et al.
In: International Journal of Molecular Sciences, Vol. 26, No. 15, 7309, 29.07.2025.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Functional Divergence of NOTCH1 and NOTCH2 in Human Cerebral Organoids Reveals Receptor-Specific Roles in Early Corticogenesis
AU - Yakovleva, Sophia
AU - Knyazeva, Anastasia
AU - Yunusova, Anastasia
AU - Allayarova, Elina
AU - Lanshakov, Dmitriy
AU - Malashicheva, Anna
AU - Shnaider, Tatiana
N1 - This study was funded by the Ministry of Science and Higher Education of the Russian Federation (state contract #075-15-2021-1063 and state project #FWNR-2022-0019).
PY - 2025/7/29
Y1 - 2025/7/29
N2 - 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, Notch1 primarily regulates early progenitor identity and neurogenesis, while Notch2 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 NOTCH1 and NOTCH2. Our findings indicate that NOTCH1 is essential for organoid growth, lumen morphogenesis, radial glial identity, and progenitor proliferation. In contrast, depleting NOTCH2 did not significantly affect these early developmental processes. These results demonstrate that NOTCH1 and NOTCH2 have potentially non-redundant and temporally distinct roles in early human corticogenesis, reflecting receptor-specific specialization within the Notch signaling pathway.
AB - 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, Notch1 primarily regulates early progenitor identity and neurogenesis, while Notch2 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 NOTCH1 and NOTCH2. Our findings indicate that NOTCH1 is essential for organoid growth, lumen morphogenesis, radial glial identity, and progenitor proliferation. In contrast, depleting NOTCH2 did not significantly affect these early developmental processes. These results demonstrate that NOTCH1 and NOTCH2 have potentially non-redundant and temporally distinct roles in early human corticogenesis, reflecting receptor-specific specialization within the Notch signaling pathway.
UR - https://www.mendeley.com/catalogue/5a28b17c-2522-3354-92b7-22ceb391c6fa/
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105013192022&origin=inward
U2 - 10.3390/ijms26157309
DO - 10.3390/ijms26157309
M3 - Article
C2 - 40806441
VL - 26
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 15
M1 - 7309
ER -
ID: 68838231