期刊
BMC BIOLOGY
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12915-016-0294-x
关键词
Cell migration; Protrusion orientation; Directionality; Persistence; Bleb; Actin-rich protrusion; Run and tumble
类别
资金
- Max Planck Society
- Medical Research Council UK
- Polish Ministry of Science and Higher Education [454/N-MPG/2009/0]
- Deutsche Forschungsgemeinschaft [HE 3231/6-1, PA 1590/1-1]
- A*Star JCO career development award [12302FG010]
- Damon Runyon fellowship award [DRG 2157-12]
- Francis Crick Institute from Cancer Research UK [FC001317]
- UK Medical Research Council [FC001317]
- Wellcome Trust [FC001317]
- Cancer Research UK [21144] Funding Source: researchfish
- Medical Research Council [MC_UU_12018/5, MC_UP_1205/1] Funding Source: researchfish
- The Francis Crick Institute [10317] Funding Source: researchfish
- MRC [MC_UU_12018/5, MC_UP_1205/1] Funding Source: UKRI
Background: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Results: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Conclusions: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.
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