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Apoptosis is involved in maintaining the character of the midbrain and the diencephalon roof plate after neural tube closure
Developmental Biology ( IF 2.5 ) Pub Date : 2020-09-30 , DOI: 10.1016/j.ydbio.2020.09.015
Yudai Matsumoto , Yoshifumi Yamaguchi , Misato Hamachi , Keiko Nonomura , Yukiko Muramatsu , Hiroki Yoshida , Masayuki Miura

Apoptosis, a major form of programmed cell death, is massively observed in neural plate border and subsequently in the roof plate (RP). While deficiency of apoptosis often results in brain malformations including exencephaly and hydrocephalus, the impact of apoptosis on RP formation and maintenance remains unclear. Here we described that mouse embryos deficient in Apaf1, a gene crucial for the intrinsic apoptotic pathway, in C57BL/6 genetic background exhibited narrow and discontinuous expression of RP marker genes in the midline of the midbrain and the diencephalon. Instead, cells positive for the neuroectodermal gene SOX1 ectopically accumulated in the midline. A lineage-tracing experiment suggests that these ectopic SOX1-positive cells began to accumulate in the midline of apoptosis-deficient embryos after E9.5. These embryos further displayed malformation of the subcommissural organ, which has been discussed in the etiology of hydrocephalus. Thus, the apoptosis machinery prevents ectopic emergence of SOX1-positive cells in the midbrain and the diencephalon RP, and helps in maintaining the character of the RP in the diencephalon and midbrain, thereby ensuring proper brain development.



中文翻译:

神经管闭合后细胞凋亡参与维持中脑和间脑顶板的特性

凋亡是程序性细胞死亡的一种主要形式,在神经板边界并随后在顶板(RP)中被大量观察到。虽然凋亡不足通常会导致脑畸形,包括脑电图和脑积水,但凋亡对RP形成和维持的影响尚不清楚。在这里我们描述了Apaf1缺陷的小鼠胚胎C57BL / 6遗传背景中对内在凋亡通路至关重要的基因,在中脑和间脑中线显示RP标记基因狭窄且不连续表达。相反,对神经外胚层基因SOX1呈阳性的细胞在中线异位积聚。谱系追踪实验表明,这些异位SOX1阳性细胞在E9.5后开始在凋亡不足的胚胎的中线积聚。这些胚胎进一步显示了连合下器官的畸形,这在脑积水的病因学中已经讨论过。因此,凋亡机制可防止中脑和中脑RP中异位出现SOX1阳性细胞,并有助于维持中脑和中脑RP的特性,从而确保大脑正常发育。

更新日期:2020-09-30
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