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Notch 介导的侧向诱导对于在内耳发育过程中维持前庭前体细胞的身份是必要的。

Notch-mediated lateral induction is necessary to maintain vestibular prosensory identity during inner ear development.

机构信息

Program in Developmental Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.

Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.

出版信息

Dev Biol. 2020 Jun 1;462(1):74-84. doi: 10.1016/j.ydbio.2020.02.015. Epub 2020 Mar 5.

Abstract

The five vestibular organs of the inner ear derive from patches of prosensory cells that express the transcription factor SOX2 and the Notch ligand JAG1. Previous work suggests that JAG1-mediated Notch signaling is both necessary and sufficient for prosensory formation and that the separation of developing prosensory patches is regulated by LMX1a, which antagonizes Notch signaling. We used an inner ear-specific deletion of the Rbpjκ gene in which Notch signaling is progressively lost from the inner ear to show that Notch signaling, is continuously required for the maintenance of prosensory fate. Loss of Notch signaling in prosensory patches causes them to shrink and ultimately disappear. We show this loss of prosensory fate is not due to cell death, but rather to the conversion of prosensory tissue into non-sensory tissue that expresses LMX1a. Notch signaling is therefore likely to stabilize, rather than induce prosensory fate.

摘要

内耳的五个前庭器官来源于表达转录因子 SOX2 和 Notch 配体 JAG1 的前感觉细胞斑块。先前的工作表明,JAG1 介导的 Notch 信号对于前感觉形成是必要且充分的,并且发育中的前感觉斑块的分离受 LMX1a 调节,后者拮抗 Notch 信号。我们使用了内耳特异性的 Rbpjκ 基因缺失,其中 Notch 信号从内耳逐渐丢失,以表明 Notch 信号对于前感觉命运的维持是持续必需的。前感觉斑块中 Notch 信号的丢失导致它们缩小并最终消失。我们表明,这种前感觉命运的丧失不是由于细胞死亡,而是由于前感觉组织转化为表达 LMX1a 的非感觉组织。因此, Notch 信号很可能稳定而不是诱导前感觉命运。

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