The Role of Claudins in Embryonic Patterning and Morphogenesis

我着迷于一个简单的单细胞受精卵转化为一个复杂的三维生物体的过程。 显然，要研究所有涉及的发育事件和过程是不可能的。 在这项资助中，我们主要关注于了解与外胚层中的细胞相邻的细胞如何决定它们是否会成为最终包围胚胎的表面外胚层或主要对中枢神经系统有贡献的神经外胚层。 这是两种截然不同的命运，必须控制多少细胞承担每种命运的平衡，以便发育能够正常进行。 我们将探讨紧密连接蛋白家族在这一决定过程中的作用。 紧密连接形成于细胞的顶端表面，在上胚层的情况下，其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，并形成一个屏障或密封，防止细胞之间的分子运动。 紧密连接蛋白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，有不同的模式的claudin表达。 这表明，在上胚层细胞层内，存在不同的微环境，它们对细胞之间可以通过的东西的选择性不同。 我们将研究这些微环境与细胞命运决定之间的关系，这些决定决定细胞是否有助于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.