β-catenin signaling marks the prospective site of primitive streak formation in the mouse embryo

β-catenin signaling marks the prospective site of primitive streak formation in the mouse embryo
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DOI:
10.1002/dvdy.20135
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发表时间:
2004-10-01
影响因子:
2.5
通讯作者:
Dufort, D
Dufort, D
中科院分区:
生物学3区
文献类型:
--
作者:
Mohamed, OA;Clarke, HJ;Dufort, D

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β-连环蛋白信号已被证明参与了几种生物的轴线形成,包括非洲爪哇和斑马鱼。遗传分析表明,Wnt/β-catenin信号通路也参与了小鼠轴的形成,因为β-catenin的靶向缺失导致胚胎在前后轴形成中受到阻碍,无法启动原肠形成,也不形成中胚层。然而,由于β-连环蛋白普遍表达,该信号通路在早期胚胎发育中活跃的确切时间和细胞类型尚不清楚。因此,为了更好地了解Wnt/β-catenin信号通路在轴形成和中胚层规范中的作用,我们研究了β-catenin在小鼠早期胚胎发育过程中的分布和信号活性。我们发现,N端非磷酸化形式的β-连环素以及β-连环素信号在第5.5天胚胎外的内脏内胚层中首次被检测到。在6.0天原肠形成开始之前,β-连环素信号不对称地分布在上胚层内,并定位于胚胎-胚外交界处附近的一小群细胞。在第6.5天及以后,在原始条纹和成熟节点中检测到β-连环蛋白信号。因此,β-连环蛋白信号先于原始条纹的形成,并且存在于将继续形成原始条纹的外胚层细胞中。这些结果支持了Wnt/β-catenin通路在哺乳动物胚胎中特定细胞形成原始条纹和结节中的关键作用,并确定了Wnt/β-catenin信号活性的一个新的结构域。(C)2004年Wiley-Liss公司
beta-Catenin signaling has been shown to be involved in triggering axis formation in several organisms, including Xenopus and zebrafish. Genetic analysis has demonstrated that the Wnt/beta-catenin signaling pathway is also involved in axis formation in the mouse, since a targeted deletion of beta-catenin results in embryos that have a block in anterior-posterior axis formation, fail to initiate gastrulation, and do not form mesoderm. However, because beta-catenin is ubiquitously expressed, the precise time and cell types in which this signaling pathway is active during early embryonic development remain unknown. Thus, to better understand the role of the Wnt/beta-catenin signaling pathway in axis formation and mesoderm specification, we have examined both the distribution and signaling activity of beta-catenin during early embryonic development in the mouse. We show that the N-terminally nonphosphorylated form of beta-catenin as well as beta-catenin signaling is first detectable in the extraembryonic visceral endoderm in day 5.5 embryos. Before the initiation of gastrulation at day 6.0, beta-catenin signaling is asymmetrically distributed within the epiblast and is localized to a small group of cells adjacent to the embryonic-extraembryonic junction. At day 6.5 and onward, beta-catenin signaling was detected in the primitive streak and mature node. Thus, beta-catenin signaling precedes primitive streak formation and is present in epiblast cells that will go on to form the primitive streak. These results support a critical role for the Wnt/beta-catenin pathway in specifying cells to form the primitive streak and node in the mammalian embryo as well as identify a novel domain of Wnt/beta-catenin signaling activity during early embryogenesis. (C) 2004 Wiley-Liss, Inc.