Trends in Cell Biology
ReviewAll Roads Lead to Directional Cell Migration
Section snippets
Directional Cell Migration
Cell migration orchestrates key events in development, homeostasis, and disease [1]. Cells can move individually [2] or as collectives [3]. The direction in which cells move is rarely random; in most cases, migration occurs in a highly directional manner, whereby cells translocate from one specific location to another. For example, immune cells move towards sites of infection; bacteria migrate toward nutrient sources; radial glia cells, germ cells, and neural crest cells migrate long distances
Principles of Cell Migration
The principal concepts underlying adherent cell migration are well understood (Figure 2) [4]. For a cell to migrate directionally it needs to become polarised, meaning the front becomes distinct from the back of the cell (Figure 2A,B). Fundamental to this breaking of symmetry is actin polymerisation at the leading edge, driving membrane outgrowth (Figure 2B), called protrusions, which adhere to the substrate by focal contacts. Bundles of actin filaments containing myosin II motors, called
How Are Stimuli Spatially Established?
Extracellular stimuli are spatially organised to direct cells to specific locations. In this section, we examine how these signals are set up.
Mechanisms of Directional Migration
In this section, we discuss the models and molecular mechanisms at play during the directional migration of cells toward these various extracellular cues.
Many Stimuli: Common Effectors?
Many of the molecular components involved in directional migration by different types of cues have been identified. However, cells are likely to be exposed to chemical, mechanical and electrical signals altogether. For example, during wound healing, chemotactic, galvanotactic, haptotactic, and durotactic migration have all been proposed to operate. Do such diverse signals ultimately control directional cell migration by common or distinct components?
Detection of these cues is inherently
Concluding Remarks
Directional migration can be controlled by a huge range of different stimuli. There are lots of avenues for future research (see Outstanding Questions) but nonetheless common themes have emerged in the establishment, regulation, and cellular response to external cues. The in vitro evidence suggests that, theoretically, signals can be spatially established and actively shaped by both migratory cells and by other source cells. To what extent this happens in vivo is still an unaddressed question.
Acknowledgments
Work in RM laboratory is supported by grants from the Medical Research Council (MR/S007792/1), Biotechnology and Biological Sciences Research Council (M008517) and Wellcome Trust (102489/Z/13/Z).
Glossary
- Arp2/3
- a protein complex that acts as an actin nucleator, allowing the formation of new actin filaments from pre-existing actin filaments.
- Cdc42
- a small GTPase involved in filopodial protrusion formation, cell polarity, actomyosin contractility, and focal adhesion assembly [123].
- Chemotaxis
- directional migration along a gradient of soluble chemical cues. The first description of chemotaxis was made by Engelmann and Pfeffer in bacteria over a century ago [124,125]. Since then, repulsive and
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