Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/β-catenin and the planar cell polarity pathways during early trunk formation in mouse
Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/β-catenin and the planar cell polarity pathways during early trunk formation in mouse
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DOI：
10.1002/dvg.20369
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发表时间：
2008-02-01
期刊：
影响因子：
1.5
通讯作者：
Shimono, Akihiko
中科院分区：
文献类型：
--
作者：
Satoh, Wataru;Matsuyama, Makoto;Shimono, Akihiko
Sfrp是一种分泌型Wnt拮抗剂，可与Wnt配体直接相互作用。我们发现Sfrp 1、Sfrp 2和Sfrp 5的失活导致早期体节小鼠胚胎中融合体节的形成，同时导致有缺陷的会聚延伸（CE），从而导致前后轴严重缩短。这些观察表明Sfrp 1，Sfrp 2和Sfrp 5在早期树干形成中的冗余作用。Sfrps的作用在Wnt途径的调节方面在遗传上是不同的。结合Sfrps突变体和环尾小鼠的遗传分析揭示了Sfrps通过调节平面细胞极性途径参与CE。此外，携带Sfrp 1纯合突变和Sfrp 2杂合突变的Dkk 1缺陷胚胎显示不规则的体节和不清楚的体节间边界，这表明Sfrps介导的Wnt/β-连环蛋白途径的抑制对于体节发生是必要的。我们的研究结果表明，Sfrps规范和非规范途径的调节是必不可少的适当的主干形成。
Sfrp is a secreted Wnt antagonist that directly interacts with Wnt ligand. We show here that inactivation of Sfrp1, Sfrp2, and Sfrp5 leads to fused somites formation in early-somite mouse embryos, simultaneously resulting in defective convergent extension (CE), which causes severe shortening of the anteroposterior axis. These observations indicate the redundant roles of Sfrp1, Sfrp2, and Sfrp5 in early trunk formation. The roles of the Sfrps were genetically distinguished in terms of the regulation of Wnt pathways. Genetic analysis combining Sfrps mutants and Loop-tail mice revealed the involvement of Sfrps in CE through the regulation of the planar cell polarity pathway. Furthermore, Dkk1-deficient embryos carrying Sfrp1 homozygous and Sfrp2 heterozygous mutations display irregular somites and indistinct intersomitic boundaries, which indicates that Sfrps-mediated inhibition of the Wnt/beta-catenin pathway is necessary for somitogenesis. Our results suggest that Sfrps regulation of the canonical and non-canonical pathways is essential for proper trunk formation.