Claudins: Critical Regulators of Epithelial Barriers and Morphogenesis

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，我们正在研究鸡胚中神经管的形成。在这个过程中，一层扁平的上皮细胞转变成一个封闭的管，上面覆盖着一层表面外胚层。我们的数据揭示了紧密连接蛋白claudin家族的新功能，它在调节细胞间离子和小分子的运动中起着重要作用。具体地说，我们表明，（i）Cldn8是细胞形状变化所必需的，允许神经外胚层弯曲以形成神经管的基部，（ii）Cldn3是非神经外胚层所必需的，以关闭神经管的顶部并将其与表面外胚层分离，以及（iii）这些claudin是将调节细胞形状变化的蛋白定位于紧密连接的细胞质面所必需的。我们的发现，即claudins是上游的分子，调节肌动蛋白细胞骨架和细胞形状的变化，是新颖的。

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.