Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Int J Mol Sci. 2022 Nov 10;23(22):13860. doi: 10.3390/ijms232213860.
Previous studies have indicated that () plays an important role in neural development and degenerative diseases. However, the bioactivity and regulatory mechanism of expression in retinal neurocytes remain unclear. In the present study, our data indicated that maintains the state of neuronal precursor cells. silencing induces differentiation in 661W cells. , a marker of precursor cells, was significantly decreased in parallel with silencing in 661W cells, whereas (), a marker of differentiated neurons, was significantly increased. Neurite outgrowth was increased by ~4.0-fold in -silenced cells. Moreover, DNA affinity purification assays and ChIP assays demonstrated that () regulates transcription in 661W cells. Silencing or overexpressing could significantly regulate the expression of and affect its promoter inducibility. Furthermore, the expression of generally occurred in parallel with that of in developing mouse retinas. Both and are expressed in the neonatal mouse retina but are developmentally silenced with age. Exogenous significantly inhibited neural activity by decreasing synaptophysin and neurite outgrowth. Thus, this study demonstrated that is transcriptionally regulated by . / silencing is involved in neuronal differentiation and maturation.
先前的研究表明,()在神经发育和退行性疾病中发挥着重要作用。然而,()在视网膜神经细胞中的生物活性和调控机制仍不清楚。本研究中,我们的数据表明,()维持神经前体细胞的状态。沉默()会诱导 661W 细胞分化。与 661W 细胞中的()沉默平行的是,神经前体细胞的标志物 ()显著降低,而分化神经元的标志物 ()显著增加。沉默()的细胞中,神经突生长增加了约 4.0 倍。此外,DNA 亲和纯化分析和 ChIP 分析表明,()在 661W 细胞中调控()的转录。沉默或过表达()可以显著调节()的表达,并影响其启动子的诱导能力。此外,在发育中的小鼠视网膜中,()的表达通常与()的表达平行。()和 ()均在新生小鼠视网膜中表达,但随年龄增长而发育沉默。外源性()通过减少突触小泡蛋白和神经突生长显著抑制神经活性。因此,本研究表明,()受 调控。/沉默参与神经元的分化和成熟。