Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus 2
Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus 2
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pygopus 2 缺陷小鼠的发育表型和 Wnt 信号传导减弱
DOI：
10.1002/dvg.20299
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发表时间：
2007-05-01
期刊：
影响因子：
1.5
通讯作者：
Dai, Xing
中科院分区：
文献类型：
--
作者：
Li, Boan;Rheaume, Catherine;Dai, Xing
典型的Wnt信号转导涉及复杂的细胞内事件，最终稳定β-连环蛋白，其进入细胞核并结合LEF/TCF转录因子以刺激基因表达。Pygopus被鉴定为果蝇中Wg（Wnt同源物）信号传导的遗传修饰剂，并且编码与β-连环蛋白/LEF/TCF复合物相关的PHD结构域蛋白。两个鼠pygopus paralogs，mpygo 1和mpygo 2，已被确定，但他们在发展和Wnt信号的作用仍然难以捉摸。在这项研究中，我们报告说，在小鼠中的mpygo 2表达的消融导致缺陷的外胚层和内胚层来源的组织，包括大脑，眼睛，毛囊和肺的形态发生。但在胚胎小肠中未观察到大体异常。使用BAT-gal报告基因，我们发现在mpygo 2不存在的情况下，大多数身体部位的Wnt信号传导减少。综上所述，我们的研究首次表明，mpygo 2缺失会影响一些但不是所有Wnt需要组织的胚胎发育。
Canonical Wnt signaling involves complex intracellular events culminating in the stabilization of beta-catenin, which enters the nucleus and binds to LEF/TCF transcription factors to stimulate gene expression. Pygopus was identified as a genetic modifier of Wg (Wnt homolog) signaling in Drosophila, and encodes a PHD domain protein that associates with the beta-catenin/LEF/TCF complex. Two murine pygopus paralogs, mpygo1 and mpygo2, have been identified, but their roles in development and Wnt signaling remain elusive. In this study, we report that ablation of mpygo2 expression in mice causes defects in morphogenesis of both ectodermally and endodermally derived tissues, including brain, eyes, hair follicles, and lung. However, no gross abnormality was observed in embryonic intestine. Using a BAT-gal reporter, we found Wnt signaling at most body sites to be reduced in the absence of mpygo2. Taken together, our studies show for the first time that mpygo2 deletion affects embryonic development of some but not all Wnt-requiring tissues.