Identifying mechanisms regulating collective cell migration

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Collective cell migration is a fundamental process in all multicellular animals and is essential for physiological functions in adults such as wound healing and immune cell surveillance, for embryonic development and during disease including metastasis. Mechanisms guiding collectively migrating cells includes sensing external guidance cues ("inputs") and generating a collective response for directional migration. These signals can be physical/mechanical, chemical and/or electrical stimuli to guide collective movements. Recent findings emphasise that mechanical stimuli and physical properties of the surrounding microenvironment are decisive factors during cell migration. Yet, our knowledge of how these factors contribute to collective cell migration within living organisms and the underlying mechanisms remain very limited.The zebrafish embryo constitutes an ideal model organism to study cell migration in vivo, as the embryos are transparent and perfectly suited for live imaging, the accessibility of cells to be transferred between different embryos, and the ease to isolate cells/tissues from the embryo for in vitro work. We will focus our research on the mesendoderm tissue, which is a cell collective that is highly conserved in vertebrates and fundamental for early embryonic development. Failures of precise collective mesendoderm migration results in embryonic defects or death. We will investigate mechanical cues and physical properties of the microenvironment that influence orientation and movement efficiency of the cell collective, and how these signals are transduced through the collective. Further we will investigate how physical barriers and adhesive surfaces contribute to cell migration. These new findings will aid our understanding of general principles of cell migration that can be applied to other multicellular systems of collective motion in physiological and disease-related context.