Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.
Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.
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DOI：
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发表时间：
2004
影响因子：
5.3
通讯作者：
Masaaki Nishiyama;K. Nakayama;R. Tsunematsu;T. Tsukiyama;A. Kikuchi;K. Nakayama
中科院分区：
文献类型：
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作者：
Masaaki Nishiyama;K. Nakayama;R. Tsunematsu;T. Tsukiyama;A. Kikuchi;K. Nakayama
Wnt信号通路在脊椎动物的早期发育和形态发生中起着关键作用。Duplin（轴复制抑制剂）与β-连环蛋白相互作用并阻止其与Tcf结合，从而抑制下游Wnt信号传导。在这里，我们表明，Duplin主要是从早期到中期的小鼠胚胎发育，我们描述了一代小鼠Duplin缺陷。Duplin（-/-）胚胎从胚胎第5.5天（E5.5）开始表现出生长迟缓，并且在E7.5时伴随着大量凋亡的发育停滞。突变胚发育成卵柱，但不形成原始条纹或中胚层。在Duplin（-/-）胚胎中，β-连环蛋白靶基因的表达，包括T（短尾畸形）、Axin 2和细胞周期蛋白D1的表达没有增加，表明发育缺陷不仅仅是由于缺乏这种抑制剂引起的Wnt信号转导上调。这些结果表明，Duplin在小鼠胚胎早期发育阶段的生长和分化中起着不可或缺的作用，可能是通过独立于抑制Wnt信号传导的机制。
The Wnt signaling pathway plays a pivotal role in vertebrate early development and morphogenesis. Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to Tcf, thereby inhibiting downstream Wnt signaling. Here we show that Duplin is expressed predominantly from early- to mid-stage mouse embryogenesis, and we describe the generation of mice deficient in Duplin. Duplin(-/-) embryos manifest growth retardation from embryonic day 5.5 (E5.5) and developmental arrest accompanied by massive apoptosis at E7.5. The mutant embryos develop into an egg cylinder but do not form a primitive streak or mesoderm. Expression of beta-catenin target genes, including those for T (brachyury), Axin2, and cyclin D1, was not increased in Duplin(-/-) embryos, suggesting that the developmental defect is not simply attributable to upregulation of Wnt signaling caused by the lack of this inhibitor. These results suggest that Duplin plays an indispensable role, likely by a mechanism independent of inhibition of Wnt signaling, in mouse embryonic growth and differentiation at an early developmental stage.