TFAP2对应物调节面部中部发育,部分是通过保留的ALX遗传通路来调节
Timothy T Nguyen1,2,3,4, Jennyfer M Mitchell5, Michaela D Kiel1,2,3
1Iowa Institute for Oral Health Research, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA 52242, USA.
概括
转录因子AP2 (TFAP2) 的对应物通过激活ALX基因来调节中面发育. 它们在小鼠中的失活会导致面部中间裂,突出显示TFAP2.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 头骨面部的发展
背景情况:
- 神经的发育依赖于基因调节网络 (GRNs).
- 面部中部的形状变化源于GRN微调,但网络激活不清楚.
研究的目的:
- 为了研究TFAP2对应物在中面神经发育中的作用.
- 确定TFAP2的下游目标和监管机制.
主要方法:
- 针对小鼠神经的Tfap2a和Tfap2b的特定无活化.
- 批量和单细胞RNA测序 (RNA-seq) 用于基因表达造型.
- 染色体免疫沉测序 (ChIP-seq) 用于识别直接的TFAP2目标.
- 斑马鱼tfap2a突变体用于跨物种验证.
主要成果:
- 协同无活化Tfap2a和Tfap2b导致面部中间裂和骨异常.
- 失去了TFAP2类型的失调中面GRN组件,包括减少ALX基因表达.
- ChIP-seq表明TFAP2家族成员对ALX基因的直接正调节.
- 在小鼠和斑马鱼中观察到TFAP2-ALX调节轴的保存.
结论:
- TFAP2对应物是脊椎动物中面发育的关键调节者.
- TFAP2蛋白激活ALX转录因子基因表达,有助于中面形态发生.
- 这一调节轴在脊椎动物中得到保护,这强调了它的基本重要性.
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