Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Development. 2023 Jul 1;150(13). doi: 10.1242/dev.201484. Epub 2023 Jun 30.
Coordinated spatio-temporal regulation of the determination and differentiation of neural stem cells is essential for brain development. Failure to integrate multiple factors leads to defective brain structures or tumour formation. Previous studies suggest changes of chromatin state are needed to direct neural stem cell differentiation, but the mechanisms are unclear. Analysis of Snr1, the Drosophila orthologue of SMARCB1, an ATP-dependent chromatin remodelling protein, identified a key role in regulating the transition of neuroepithelial cells into neural stem cells and subsequent differentiation of neural stem cells into the cells needed to build the brain. Loss of Snr1 in neuroepithelial cells leads to premature neural stem cell formation. Additionally, loss of Snr1 in neural stem cells results in inappropriate perdurance of neural stem cells into adulthood. Snr1 reduction in neuroepithelial or neural stem cells leads to the differential expression of target genes. We find that Snr1 is associated with the actively transcribed chromatin region of these target genes. Thus, Snr1 likely regulates the chromatin state in neuroepithelial cells and maintains chromatin state in neural stem cells for proper brain development.
神经干细胞的定型和分化的时空协调调节对于大脑发育至关重要。如果不能整合多种因素，就会导致大脑结构缺陷或肿瘤形成。先前的研究表明，需要改变染色质状态来指导神经干细胞分化，但机制尚不清楚。对果蝇中 SMARCB1 同源物 Snr1 的分析表明，它在调节神经上皮细胞向神经干细胞的转变以及随后的神经干细胞向构建大脑所需的细胞的分化中起关键作用。神经上皮细胞中 Snr1 的缺失会导致神经干细胞过早形成。此外，神经干细胞中 Snr1 的缺失会导致神经干细胞在成年期持续存在。神经上皮细胞或神经干细胞中 Snr1 的减少会导致靶基因的差异表达。我们发现 Snr1 与这些靶基因的活跃转录染色质区域相关联。因此，Snr1 可能调节神经上皮细胞中的染色质状态，并维持神经干细胞中的染色质状态，以实现正常的大脑发育。
