Claudins: Critical Regulators of Epithelial Barriers and Morphogenesis

Claudins：上皮屏障和形态发生的关键调节因子

• 批准号: RGPIN-2017-05323
• 负责人: Ryan, Aimee
• 金额: $ 2.48万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629059
• 关键词: Claudins; Critical; Regulators; Epithelial; Barriers

Our goal is to understand how simple epithelial cell layers are transformed into complex 3D shapes. To do this, we are studying neural tube formation in the chick embryo. During this process, a flat sheet of epithelial cells is transformed into a closed tube with an overlying layer of surface ectoderm. Our data revealed new functions the claudin family of tight junction proteins that have an essential role in regulating the movement of ions and small molecules between cells. Specifically, we showed that (i) Cldn8 is required for cell shape changes that allow the neural ectoderm to bend to form the base of the neural tube, (ii) Cldn3 is required in the non-neural ectoderm to close the top of the neural tube and separate it from the surface ectoderm, and (iii) these claudins are required to localize proteins that regulate cell shape changes to the cytoplasmic face of tight junctions. Our findings, that claudins are upstream of molecules that regulate the actin-cytoskeleton and cell-shape changes, are novel.

我们的目标是了解简单的上皮细胞层如何转化为复杂的 3D 形状。为此，我们正在研究鸡胚胎中神经管的形成。在此过程中，上皮细胞的扁平片转变为具有表面外胚层覆盖层的封闭管。我们的数据揭示了紧密连接蛋白claudin家族的新功能，它们在调节细胞间离子和小分子的运动方面发挥着重要作用。具体来说，我们发现（i）细胞形状变化需要 Cldn8，使神经外胚层弯曲以形成神经管的底部；（ii）非神经外胚层需要 Cldn3 来封闭神经管顶部并将其与表面外胚层分离；（iii）这些紧密蛋白需要将调节细胞形状变化的蛋白质定位到紧密神经管的细胞质面。 路口。我们的发现是新颖的，即紧密蛋白是调节肌动蛋白细胞骨架和细胞形状变化的分子的上游。