Ectodermal Wnt signaling regulates abdominal myogenesis during ventral body wall development.

Ectodermal Wnt signaling regulates abdominal myogenesis during ventral body wall development.
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外胚层 Wnt 信号在腹侧体壁发育过程中调节腹部肌生成。

DOI:
10.1016/j.ydbio.2013.12.027
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发表时间:
2014-03
影响因子:
2.7
通讯作者:
Guo, Xizhi
Guo, Xizhi
中科院分区:
生物学3区
文献类型:
--
作者:
Wang, Lifang;Zhou, Rujiang;Yao, Zhengju;Guo, Xizhi

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腹侧体壁缺陷是常见的出生异常,其特征是体壁闭合缺陷、腹部肌肉组织发育不全和各种器官的多处畸形。然而,腹体壁缺陷的机制仍然难以捉摸。在此,我们通过灭活小鼠腹部外胚层的Wlsor β-catenin来研究Wnt信号在腹体壁发育中的作用。在胚胎发育过程中,腹侧上皮中Wl的缺失阻断了Wnt蛋白的分泌,导致腹侧肌肉系统和生殖泌尿道发育不良。分子分析显示,真皮和肌分化的基础间充质祖细胞受到干扰的外胚层Wls的损失。Wnt-Pitx 2轴的活性受损的腹侧间充质的突变体体壁,这部分占腹侧肌肉组织形成的缺陷。相比之下,β-连环蛋白或Wnt 5a的上皮缺失与外胚层Wl突变体中的体壁缺陷不相似。这些研究结果表明,外胚层Wnt信号指示腹体壁发育过程中的中胚层规格和腹部肌肉组织形成,为外胚层间充质信号是腹体壁缺陷起源的潜在统一机制的理论提供了证据。
Defects of the ventral body wall are prevalent birth anomalies marked by deficiencies in body wall closure, hypoplasia of the abdominal musculature and multiple malformations across a gamut of organs. However, the mechanisms underlying ventral body wall defects remain elusive. Here, we investigated the role of Wnt signaling in ventral body wall development by inactivatingWlsorβ-cateninin murine abdominal ectoderm. The loss ofWlsin the ventral epithelium, which blocks the secretion of Wnt proteins, resulted in dysgenesis of ventral musculature and genito-urinary tract during embryonic development. Molecular analyses revealed that the dermis and myogenic differentiation in the underlying mesenchymal progenitor cells was perturbed by the loss of ectodermalWls. The activity of the Wnt-Pitx2 axis was impaired in the ventral mesenchyme of the mutant body wall, which partially accounted for the defects in ventral musculature formation. In contrast, epithelial depletion ofβ-cateninorWnt5adid not resemble the body wall defects in the ectodermalWlsmutant. These findings indicate that ectodermal Wnt signaling instructs the underlying mesodermal specification and abdominal musculature formation during ventral body wall development, adding evidence to the theory that ectoderm-mesenchyme signaling is a potential unifying mechanism for the origin of ventral body wall defects.
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