Signaling platforms and structures required for cell motility and guided cell migration

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The control over the mechanisms facilitating cell motility acquisition, and loss of migratory behavior is important for a range of biological processes such as organ morphogenesis, tissue repair and maintenance and immune response. These processes are also relevant for pathological conditions such as cancer metastasis and inflammation. A useful in vivo model for investigating those processes is the migration of Primordial Germ Cells (PGCs). These cells perform long-range single-cell migration from their site of specification to the region where the cease migrating and participate in organ formation. In the first part of project we have characterized the mechanisms facilitating polarization of cells as they exit from apolar states and start migrating. In this application for continuing the project, we propose to investigate the other side of the process i.e. the cellular and molecular mechanisms that contribute to the loss of polarity. This issue will be investigated during embryonic development, when the cells undergo processes of cell polarity loss during several stages of their migration. The proposed work involves analysis and manipulation of the distribution of relevant molecules within the cells, a range of manipulations in the activity of signaling pathways and live imaging of the processes. Together, these investigations will shed light on a relatively less understood process in cell and developmental biology – the loss of cell polarity.