The Role of Claudins in Embryonic Patterning and Morphogenesis

我着迷于将一个简单的单细胞受精卵转化为复杂的三维生物体的过程。显然，不可能研究所有与之相关的发展事件和过程。在这项资助中，我们主要集中于了解外胚层中相邻的细胞如何决定它们是否会成为最终包裹胚胎的表面外胚层或主要有助于中枢神经系统的神经外胚层。这是两种截然不同的命运，必须控制细胞数量的平衡，才能使发育正常进行。我们将探讨紧密连接蛋白的claudin家族在这个决策过程中的作用。细胞的顶端表面形成紧密的连接，在外胚层的情况下，它与胚外环境直接接触。紧密连接的作用是将细胞彼此连接起来，并形成屏障或密封，阻止细胞之间的分子运动。claudin是紧密连接的一个组成部分，事实上，它们决定了细胞之间的密封有多紧密，以及什么类型的分子可以在细胞之间通过。我们发现在外胚层中，有不同的claudin表达模式。这表明，在外胚层细胞层内，不同的微环境对细胞间传递的选择性不同。我们将研究这些微环境与细胞命运决定之间的关系，这些决定决定了细胞是否会形成神经外胚层或表面外胚层。

I am fascinated by the processes that direct the conversion of a simple one-cell fertilized egg into a complex three dimensional organism. Obviously, it is impossible to study all of the developmental events and processes that are involved. In this grant we are primarily focusing on understanding how cells that are adjacent to one in the epiblast determine whether they will become surface ectoderm that will eventually enclose the embryo or neural ectoderm that will contribute primarily to the central nervous system. These are two dramatically different fates and the balance of how many cells assume each fate must be controlled so that development can proceed normally. We are going to explore the role of the claudin family of tight junction proteins in this decision process. Tight junctions form at the apical surface of the cell, which in the case of the epiblast is in direct contact with the extraembryonic environment. Tight junctions act to link the cells to one another and create a barrier or seal that prevents the movement of molecules between the cells. Claudins are an integral component of the tight junction and in fact, they determine how tight a seal is made between the cells and what types of molecules can pass between the cells. We discovered that in the epiblast, there are different patterns of claudin expression. This suggests that within the epiblast cell layer, there are different micro-environments that differ in their selectivity of what can pass between the cells. We are going to investigate the relationship between these microenvironments and the cell fate decisions that determine whether a cell will contribute to the neural ectoderm or the surface ectoderm.