The aberrant canonical Wnt-β-catenin signaling can cause devastating outcomes of tissue morphogenesis and tumor formation. In this study, we examined the impact of overexpression of constitutive active β-catenin in mouse periocular neural crest-derived mesenchymal cells during embryonic eyelid morphogenesis. We expressed a stabilized β-catenin in which the exon 3 of the 1 gene was deleted in periocular neural crest (PONC)-derived eyelid stromal cells (). Histopathological examinations were performed to examine the eyelid morphogenetic alterations in mice. Immunohistochemical investigations for cell proliferation, apoptosis, and differentiation were also assessed. We discovered that nuclear accumulation of β-catenin resulted in a reduction of nuclear Ki-67 and phospho-Erk1/2 expression levels and elevation of apoptosis in PONC cells during embryonic eyelid closure morphogenesis. Interestingly, however, the eyelid epithelial migration was not affected, which resulted in only eyelid epidermal closure but lacked underneath dermal formation at embryonic (E) day 16.5. The sequelae of revealed the malformation of the eyelid margin and Meibomian gland and deficiency of Muller's smooth muscle fibers formation. Consequently, mice manifested blepharophimosis syndrome at P21. Our data suggested that aberrant expression of β-catenin gain of function in PONC interrupts the interplay between epithelium and stroma for the morphogenesis of eyelid closure during embryonic development.

中文翻译：

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小鼠眼周神经嵴衍生间充质细胞中的β-连环蛋白功能获得突变体损害胚胎眼睑形态发生并导致小鼠眼睑裂综合征


异常的经典 Wnt-β-连环蛋白信号传导可能导致组织形态发生和肿瘤形成的破坏性结果。在这项研究中，我们研究了胚胎眼睑形态发生过程中小鼠眼周神经嵴衍生间充质细胞中组成型活性β-连环蛋白过度表达的影响。我们表达了一种稳定的 β-连环蛋白，其中 1 基因的外显子 3 在眼周神经嵴 (PONC) 来源的眼睑基质细胞中被删除 ()。进行组织病理学检查以检查小鼠眼睑形态发生的变化。还评估了细胞增殖、凋亡和分化的免疫组织化学研究。我们发现，在胚胎眼睑闭合形态发生过程中，β-连环蛋白的核积累导致核 Ki-67 和磷酸化 Erk1/2 表达水平降低，以及 PONC 细胞凋亡增加。然而有趣的是，眼睑上皮迁移并未受到影响，这导致在胚胎 (E) 第 16.5 天仅眼睑表皮闭合，但缺乏真皮下的形成。后遗症表现为眼睑边缘和睑板腺畸形以及Muller平滑肌纤维形成缺陷。因此，小鼠在 P21 时表现出眼睑裂痕综合征。我们的数据表明，PONC 中 β-连环蛋白功能增益的异常表达中断了胚胎发育过程中眼睑闭合形态发生的上皮和基质之间的相互作用。