Calcium signaling and formation of cellular protrusions in zebrafish germ-cell migration

在有性生殖的生物体中，原始生殖细胞（PGCs）产生配子，配子负责下一代新生物体的发育。原始生殖细胞的一个重要特征是它们从指定的位置迁移到性腺的位置，在那里它们分化成配子。这种行为可以作为多细胞生物中细胞迁移的一般体内模型，目的是了解控制细胞运动和定向迁移的机制。虽然已知引导细胞的信号和结合它的受体（分别为SDF-1a和CXCR4b），但导致细胞极化和定向迁移的确切下游信号事件尚不清楚。我们发现钙调节肌球蛋白收缩促进细胞突起的形成，而CXCR4的激活将这一过程引导到细胞的前沿。更具体地说，肌球蛋白收缩导致细胞膜与细胞皮层分离，从而促进细胞质流动和形成泡的扩张。本研究计划的目标是进一步研究水泡形成的分子和细胞机制，并探索细胞运动开始时发生的相关事件。

In sexually reproducing organisms, primordial germ cells (PGCs) give rise to gametes that are responsible for the development of a new organism in the next generation. An important feature of primordial germ cells is that they migrate from the position where they are specified towards the position of the gonad where they differentiate into gametes. This behavior serves as a general in vivo model for cell migration in multi-cellular organisms with the aim of understanding the mechanisms controlling cell motility and directional migration. Whereas the signal that guides the cells and the receptor that binds it are known (SDF-1a and CXCR4b respectively) the precise downstream signaling events leading to cell polarization and directed migration are not known. We have found that calcium regulated myosin contraction powers the formation of cellular protrusions and that activation of CXCR4 directs this process to the leading edge of the cell. More specifically, myosin contraction results in the separation of the membrane from the cell cortex that facilitates cytoplasmic flow and expansion of the forming bleb. The goal of this research proposal is to further investigate the molecular and cellular mechanisms responsible bleb formation and to explore the relevant events occurring at the onset of cell motility.