TFAP2对应基调调节面部中部发育,部分通过一个保留的ALX遗传通路
Timothy T Nguyen1,2,3,4, Jennyfer M Mitchell5, Michaela D Kiel1,2,3
1Iowa Institute for Oral Health Research, College of Dentistry & Dental Clinics, University of Iowa, Iowa City, IA, 52242, USA.
bioRxiv : the preprint server for biology
|July 3, 2023
概括
转录因子AP2 (TFAP2) 对于面部中部发育至关重要. 它对ALX基因的调节对于预防脊椎动物中部面部裂和骨异常至关重要.
科学领域:
- 发育生物学是发展生物学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 神经的发育依赖于基因调节网络 (GRNs).
- 了解面部中部GRN激活和连接是有限的.
- 面部形状的变化是由微调GRN组件引起的.
研究的目的:
- 研究转录因子AP2 (TFAP2) 家族成员在小鼠中面发育中的作用.
- 阐明TFAP2调节中面融合和模式的分子机制.
主要方法:
- 产生了针对Tfap2a和Tfap2b的小鼠神经的特定条件淘汰.
- 使用批量和单细胞RNA测序 (RNA-seq) 来分析基因表达变化.
- 执行染色体免疫沉测序 (ChIP-seq) 来识别直接的TFAP2目标.
主要成果:
- 对Tfap2a和Tfap2b的协同无活化导致了面部中间裂和骨异常.
- 丢失TFAP2失调了关键的面部中部GRN组件,包括降低了Alx1/3/4 (Alx) 转录水平.
- TFAP2直接和积极调节Alx基因表达,这是小鼠和斑马鱼中保存的机制.
结论:
- TFAP2在脊椎动物中脸部发育中起着至关重要的作用.
- TFAP2通过控制ALX转录因子基因表达来调节中脸部发育.
- 这项研究阐明了面发育中的关键调节机制.
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