Chemokine-biased robust self-organizing polarization of migrating cells in vivo
Open Access
- 11 February 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (7)
- https://doi.org/10.1073/pnas.2018480118
Abstract
To study the mechanisms controlling front-rear polarity in migrating cells, we used zebrafish primordial germ cells (PGCs) as an in vivo model. We find that polarity of bleb-driven migrating cells can be initiated at the cell front, as manifested by actin accumulation at the future leading edge and myosin-dependent retrograde actin flow toward the other side of the cell. In such cases, the definition of the cell front, from which bleb-inhibiting proteins such as Ezrin are depleted, precedes the establishment of the cell rear, where those proteins accumulate. Conversely, following cell division, the accumulation of Ezrin at the cleavage plane is the first sign for cell polarity and this aspect of the cell becomes the cell back. Together, the antagonistic interactions between the cell front and back lead to a robust polarization of the cell. Furthermore, we show that chemokine signaling can bias the establishment of the front-rear axis of the cell, thereby guiding the migrating cells toward sites of higher levels of the attractant. We compare these results to a theoretical model according to which a critical value of actin treadmilling flow can initiate a positive feedback loop that leads to the generation of the front-rear axis and to stable cell polarization. Together, our in vivo findings and the mathematical model, provide an explanation for the observed nonoriented migration of primordial germ cells in the absence of the guidance cue, as well as for the directed migration toward the region where the gonad develops.Funding Information
- EC | FP7 | FP7 Ideas: European Research Council (CellMig 268806)
- Deutsche Forschungsgemeinschaft (RA863)
- Deutsche Forschungsgemeinschaft (SFB 1348)
- Israel Science Foundation (1459/17)
- EC | FP7 | FP7 Ideas: European Research Council (PolarizeMe 771201)
- Deutsche Forschungsgemeinschaft (EXC 1003-CIM)
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