Cytoskeletal/junction relationships during epithelial remodeling events

细胞表面是细胞与其环境之间的界面。该界面的相互作用使细胞能够产生运动、呈现特定形状、执行特定功能并形成多细胞结构。毫不奇怪，动物细胞内细胞骨架的主要元件与细胞表面相关，特别是涉及与邻近细胞和支撑基质形成连接的表面区域。我的研究计划的长期目标是探索组织环境中细胞间连接和细胞骨架之间的相互作用，并确定这两个系统如何共同发挥作用，在动物体内许多管和腔的细胞层（上皮细胞）中产生复杂的重塑事件。我们特别感兴趣的是细胞骨架和连接如何相互作用，使细胞与相邻细胞分离，并通过上皮从身体的一个区室移动到另一个区室。在接下来的五年中，我们将探索细胞骨架和连接的功能机制，以将发育中的精子细胞移动通过哺乳动物睾丸的生精上皮，并从该上皮中释放完全形成的精子细胞。我们将重点关注与细胞骨架相关的管状结构，我们认为它们是亚细胞机器，在精子细胞产生过程中发生的广泛上皮重塑事件中内化和降解完整的细胞间连接。我们将在分子水平上表征这些结构，并确定它们的功能是否是下一代发育中的精子细胞成功地进一步进入上皮细胞所必需的。我们的结果已经使生物学家如何看待与精子释放相关的连接解体发生了范式转变。在接下来的几年里，我们预计我们的结果将产生类似的转变，生物学家如何看待下一代发育中的精子细胞在生精上皮中从一个隔室到另一个隔室的运动。

The cell surface is the interface between cells and their environment. Interactions at this interface enable cells to generate movement, to assume specific shapes, to carry out specific functions, and to form multicellular structures. It is not surprising that major elements of the cytoskeleton within animal cells are related to the cell surface, particularly to regions of the surface involved in forming connections both with neighboring cells and with supporting substrates. The long-term objective of my research program is to explore the interaction between intercellular junctions and the cytoskeleton in cells within the context of tissues, and determine how the two systems function together to generate complex remodeling events in cell layers (epithelia) that line the many tubes and cavities in animals. We are particularly interested in how the cytoskeleton and junctions interact to allow cells to detach from their neighbors and to move through epithelia from one compartment of the body to another. Over the next five years we will explore the mechanism by which the cytoskeleton and junctions function to move developing sperm cells through the seminiferous epithelium of the mammalian testis, and to release fully formed sperm cells from this epithelium. We will focus on cytoskeleton-related tubular structures that we propose are sub-cellular machines that internalize and degrade intact intercellular junctions during the extensive epithelial remodeling events that occur during the production of sperm cells. We will characterize these structures at the molecular level and determine if their function is required for the successful movement of the next generation of developing sperm cells further into the epithelium. Our results have already generated a paradigm shift in how biologists view junction disassembly related to sperm release. Over the next few years we anticipate that our results will generate a similar shift in how biologists view the movement of the next generation of developing sperm cells from one compartment to another in the seminiferous epithelium.