Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes
Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes
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DOI：
10.1073/pnas.0607779104
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发表时间：
2007-04-03
影响因子：
11.1
通讯作者：
Matsuo, Isao
中科院分区：
文献类型：
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作者：
Kimura-Yoshida, Chiharu;Tian, E.;Matsuo, Isao
前脏内胚层（AVE）在小鼠早期胚胎的前后轴发育中起着至关重要的作用。为了评估参与AVE形成的基因级联反应，通过制备转基因小鼠分析了调控脊椎动物Otx2基因在AVE中表达的顺式调控元件。AVE中的Otx2表达直接受叉头转录因子Foxa2调控。此外，在原条前期到早期阶段，Foxa2对于内脏内胚层中Wnt拮抗剂Dkk1和Cerl的表达是必不可少的；然而，Foxa2对于随后与前脑诱导相关的Dkk1表达似乎是可有可无的。因此，我们提出，就AVE特异性基因表达的调控而言，Foxa2在早期前后轴极化中至关重要。这些发现为Foxa2转录因子在脊索动物身体结构进化过程中在前部特化方面的保守作用提供了深刻的见解。
Anterior visceral endoderm (AVE) plays essential roles with respect to anterior-posterior axis development in the early mouse embryo. To assess the genetic cascade involved in AVE formation, the cis-regulatory elements directing expression of vertebrate Otx2 genes in the AVE were analyzed via generation of transgenic mice. Otx2 expression in AVE is regulated directly by the forkhead transcription factor, Foxa2. Moreover, Foxa2 is essential for expression of the Wnt antagonists, Dkk1 and Cerl, in visceral endoderm during the pre- to early streak stages; however, Foxa2 appears to be dispensable for subsequent Dkk1 expression associated with forebrain induction. Thus, we propose that Foxa2 is crucial in early anterior-posterior axis polarization in terms of regulation of expression of AVE-specific genes. These findings provide profound insights into conserved roles of Foxa2 transcription factors in anterior specification throughout the evolution of the chordate body plan.