A Spatiotemporal Requirement for Prickle 1-Mediated PCP Signaling in Eyelid Morphogenesis and Homeostasis
A Spatiotemporal Requirement for Prickle 1-Mediated PCP Signaling in Eyelid Morphogenesis and Homeostasis
复制标题
Prickle 1 介导的 PCP 信号在眼睑形态发生和稳态中的时空要求
DOI：
10.1167/iovs.17-22947
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发表时间：
2018-02-01
影响因子：
4.4
通讯作者：
Liu, Chunqiao
中科院分区：
文献类型：
--
作者：
Guo, Dianlei;Yuan, Zhaohui;Liu, Chunqiao
目的.组织闭合/融合是器官发生过程中的基本过程，部分由Wnt/平面细胞极性（Wnt/PCP）途径驱动。本研究通过分析缺乏Prickle 1（PCP的核心成分）的小鼠以及Prickle 1依赖的眼睑发育信号网络，探索PCP信号在眼睑发育中的时空方面。培育了具有亚型和无效等位基因的野生型和Prickle 1复合突变小鼠，并用于研究眼睑形态发生。通过组织切片的光学显微镜和扫描电镜检查胚胎眼睑融合和出生后重新打开的时间过程。免疫组织化学进行监测细胞增殖，死亡，并通过产前和产后眼睑发育的分子身份。Prickle 1突变体胚胎在胚胎期眼睑闭合延迟，但出生后表现为眼睑过早重新打开，随后出现角膜畸形。突变胚胎显示下调磷酸化的c-Jun，和上调增加的β-连环蛋白在眼睑前区的单独的细胞群体。在出生后的突变体眼睑重新打开之前，观察到细胞死亡增加和间充质浸润减少。虽然在许多组织中广泛表达，但在E15.5时，Prickle 1在空间上仅限于眼睑前部，在此位置，c-Jun和β-连环蛋白表达在Prickle 1突变体中发生改变。这项研究表明，在眼睑形态发生和稳态的时空要求刺1介导的PCP信号。该研究将Prickle 1介导的PCP信号传导与现有网络联系起来，并为研究先天性眼表疾病提供了有用的动物模型。
PURPOSE. Tissue closure/fusion is a fundamental process during organogenesis, driven in part by the Wnt/planar cell polarity (Wnt/PCP) pathway. This study explored the spatial and temporal aspects of PCP signaling in eyelid development through analysis of mice lacking Prickle 1, a core PCP component, and the Prickle1-dependent signaling networks underlying eyelid development.METHODS. Wild type and Prickle 1 compound mutant mice with a hypomorphic and a null allele were bred and used to study eyelid morphogenesis. The time course of embryonic eyelid fusion and postnatal reopening was examined by light microscopy of tissue sections and scanning electron microscopy. Immunohistochemistry was conducted to monitor cell proliferation, death, and molecular identities through pre-and postnatal eyelid development.RESULTS. Prickle 1 mutant embryos exhibited a profound delay in eyelid closure at embryonic ages, but manifested precocious eyelid reopening postnatally, with ensuing cornea malformation. Mutant embryonic showed downregulation of phosphorylated c-Jun, and upregulation of increased beta-catenin in separate cell populations of the eyelid front area. Increased cell death and decreased mesenchymal infiltration was observed in postnatal mutant eyelid prior to eyelid reopening. While broadly expressed in many tissues, Prickle 1 was spatially restricted to the eyelid front at E15.5, a location where c-Jun and beta-catenin expression was altered in Prickle 1 mutants.CONCLUSIONS. The study demonstrates a spatiotemporal requirement for Prickle 1-mediated PCP signaling during eyelid morphogenesis and homeostasis. The study links Prickle 1-mediated PCP signaling to existing networks, and provides a useful animal model for studying congenital ocular surface diseases.