Abnormal development of central nervous system (CNS) caused by neural tube defects is not only a major contributor in the prevalence of stillbirths and neonatal deaths but also causes lifelong physical disability in surviving infants. Due to insufficient known investigated causes, CNS developmental abnormality has brought sever burden on health around the world. From previous results of high throughput transcriptome sequencing, we selected transcription factor Nkx2.1 as a candidate to investigate its role on brain abnormalities induced by excessive retinoic acid. The result of in situ hybridization showed that Nkx2.1 was mainly expressed in mouse brain. After the Nkx2.1 gene was silenced, retarded proliferation and accelerated apoptosis were found in mouse Neuro-2a (N2a) cells. Furthermore, our results indicated that the main components of sonic hedgehog (Shh) signaling pathway were affected in Nkx2.1-silenced cells, implying that Nkx2.1 plays an important role in the development of mouse brain by regulating Shh signaling pathway.

中文翻译：

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Nkx2.1的下调与过量视黄酸引起的大脑异常有关。

由神经管缺陷引起的中枢神经系统（CNS）异常发育不仅是死产和新生儿死亡的主要原因，而且还导致存活婴儿的终生身体残疾。由于已知原因不足，中枢神经系统发育异常给全世界的健康带来了沉重负担。从高通量转录组测序的先前结果中，我们选择转录因子Nkx2.1作为候选基因，以研究其在过量视黄酸诱导的脑异常中的作用。结果原位杂交显示NKX2.1主要表达在小鼠大脑。后NKX2.1该基因被沉默，在小鼠Neuro-2a（N2a）细胞中发现了延迟的增殖和加速的凋亡。此外，我们的结果表明，声波刺猬（Shh）信号通路的主要成分在Nkx2.1沉默的细胞中受到影响，这表明Nkx2.1通过调节Shh信号通路在小鼠大脑发育中起重要作用。