在哺乳动物平衡器官的成熟过程中,Notch1是维持支持细胞身份和前庭功能所需的
Alison Heffer1, Choongheon Lee2, Joseph C Holt2,3
1Flaum Eye Institute, Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York, 14642, USA.
bioRxiv : the preprint server for biology
|July 1, 2024
概括
Notch1对于前体发育至关重要. 在小鼠中,删除Notch1会导致支持细胞转化为毛细胞,损害平衡功能和感官唤起的潜能.
科学领域:
- 内耳生物学 内耳生物学
- 发育神经科学的发展神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 内耳包含听觉 (耳) 和前庭器官,两者都使用毛发和支细胞.
- 在出生后,Notch1对于支持大中的细胞存活至关重要.
- 诺奇1在前置器官成熟中的作用尚不清楚.
研究的目的:
- 研究Notch1在前置器官发育和成熟中的功能.
- 为了确定是否需要Notch1来维持前庭支细胞的存活.
- 分析Notch1删除对前庭感官功能和行为的影响.
主要方法:
- 在小鼠的Sox2-表达前体细胞中,在P0/P1.1.时条件删除了Notch1.
- 对前置器官结构的组织学分析.前置器官结构.
- 评估毛细胞发育和支持细胞存活的情况.
- 测量前庭感官唤起潜力 (VsEPs).
- 行为测试 (平衡束,强迫游泳测试).
主要成果:
- 诺奇1删除导致前庭支细胞的损失,这些细胞转化为II型毛细胞.
- 这些转换的毛细胞存活到成年.
- 垂体感官唤起潜能 (VsEPs) 被废除,表明失去了状功能.
- 状体中的I型毛细胞未能发展出特征性的玻璃杯.
- 突变小鼠表现出失衡和与前体相关的行为.
结论:
- 垂体支细胞可以在Notch1损失时转化为毛细胞,而不是尾细胞.
- 诺奇1对于产后前置细胞成熟,状细胞发育和功能至关重要.
- 这种转换和毛细胞的存活发生,尽管支持细胞减少,影响整体前庭细胞的能力.
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