Cell motility in vivo - polarization of zebrafish germ cells

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A central theme in Developmental Biology is the movement of cells and tissues during pattern formation and organogenesis. Determining the molecular and cellular mechanisms facilitating cell polarization and migration in vivo would thus contribute to our understanding of various developmental processes. The migration of zebrafish primordial germ cells serves as an excellent accessible in vivo model for cell migration. The migration path of these cells, the molecules responsible for directing them and some of the cellular mechanisms facilitating cell motility are known. This knowledge will be employed in the proposed research that is aimed at addressing the issue of the acquisition of cell polarity in the context of cell motility. Filopodia are thin cellular extensions containing parallel actin filaments that are often observed on the surface of migratory cells. Whereas filopodia are thought to play a role in cell migration, their precise function in the context of the intact organism is so far unknown. In the course of this study, the distribution and the morphology of filopodia will be monitored during different steps of the migration process (acquisition of motility, directed migration and stop upon arrival at the target). The distribution of different regulators and structural proteins in the filopodia will then be determined at those different phases of migration. In the next step, over-expression or expression of modified protein versions will be used to affect filopodia development (filopodia distribution, length and stability). The effect of alterations in filopodia structure on biochemical pathways (calcium signaling, actin distribution, septin polarization and the activation patterns of RhoGTPases) important for cell motility will be determined. Last, dynamic parameters of cell migration will be compared between wild-type cells and cells in which filopodia development is compromised. Specifically, we will examine the effect of abnormal filopodia on cell migration speed, maintenance of direction and arrival at the target.