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Updated: May 7, 2026

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Zfp750可以防止口腔粘附,并促进暂时的上皮质融合
bioRxiv : the preprint server for biology
|February 23, 2026
概括
ZNF750突变不是口腔口腔裂 (OFC) 的主要原因. 然而,Zfp750对外皮发育至关重要,对于适当的胚胎融合和分离事件至关重要.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 角质细胞分化成包括外皮在内的基层是由转录因子调节的.
- 像TP63,IRF6和GRHL3这样的转录因子中的突变会扰乱外皮发育和胚胎融合事件,导致诸如耳面裂 (OFC) 这样的情况.
- 已知ZNF750在角质细胞分化中的作用,但其对OFC风险的贡献及其在外皮发育中的功能仍然不清楚.
研究的目的:
- 调查ZNF750突变是否有助于 orofacial 裂的风险.
- 确定Zfp750在外皮发育中的作用及其对胚胎形态遗传事件的影响.
主要方法:
- 在5,659个个体中测序ZNF750基因,包括2,125个非综合征性OFC.
- 在变种病原性和评估变种从父母传染给受影响的孩子的形预测.
- 使用斑马鱼和小鼠模型进行功能性测试,包括生成Zfp750框架转移突变小鼠.
- 对Zfp750突变胚胎的RNA测序和免疫光分析.
主要成果:
- 确定了33种罕见的ZNF750误解变体,预计约有一半是有害的;然而,这些变体在OFC病例中没有显著过度传播.
- 斑马鱼测试显示,两种变体的活性降低,但在相应的小鼠模型中没有观察到表型.
- Zfp750框架转移突变小鼠表现出口内粘附和暂时上皮融合的缺失,与缺陷外皮发育相关的表型.
- RNA测序揭示了突变胚胎中的表皮分化和外皮基因的改变表达,口腔粘附中存在外皮蛋白.
结论:
- 在ZNF750中发生的突变不是 orofacial 裂风险的显著遗传因素.
- Zfp750在外皮的发育中起着至关重要的作用,影响重要的胚胎形态遗传过程,如 palatogenesis 和临时上皮融合的形成.
- 这些发现凸显了Zfp750在依赖外皮的发育过程中的重要性.
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