Cell Migration during Development

Abstract

Cell migration is essential during the establishment of a three‐dimensional and multilayered organism. These migratory processes are highly coordinated both in time and space through various intercellular and cell–substrate interactions. Cells, moving either individually or as cohorts, use specific permissive, restrictive, attractive or repulsive guidance cues in their surroundings to move to their final destinations. These cues, which are mostly dynamic, induce specific intracellular responses in the receiving cells and often have direct effects on the cytoskeleton. These signals result in the acquisition of motile behaviour and allow detachment from the surrounding cells or tissue. They further lead to the establishment of cell or tissue polarity and induce directionality in the migration. The molecular nature of the guidance cues during embryonic, larval and foetal development is often analogous in diverse settings of cell migration.

Key Concepts:

  • Cells follow specific migration routes during development.

  • Cells can migrate either individually or in groups.

  • Surrounding guidance cues guide the migrating cells.

  • Guidance cues can be restrictive versus permissive and attractive versus repulsive.

  • Guidance cues induce specific intracellular signalling responses.

  • Intracellular polarity defines the direction of migration.

  • Collective migration requires molecular interactions between the migrating cells.

  • Contact inhibition of locomotion affects the coordinated motile behaviour of cranial neural crest cells.

Keywords: pathfinding; chemotaxis; morphogenetic movements; germ cell migration; neural crest cells

Figure 1.

Migration is mediated by attractive and repulsive cues. Schematic representation of a cell moving on a substrate (a–c) and within a cell layer or tissue (d and e). (a) Cells can migrate either up (green arrow) or down (red arrow) the chemotactic gradient. (b) Specific components present in the ECM may provide permissive or nonpermissive cues for the migratory cells. (c) During the process of haptotaxis, cells move along an adhesive gradient towards the area of the strongest adhesion. (d and e) Cells moving between other cells can use guidance cues presented by the surrounding cells via direct intercellular contact.

Figure 2.

Multiple ways of pathfinding during migration. (a) Cells can migrate to their final destination via intermediate steps, using consecutive gradients of attractive factors (green circles). While finding their way, cells can stop at intermediate points to reorient themselves and then move along the next gradient. (b) Migrating cells can also be correctly positioned by the combined activity of repulsive gradients (red circles). (c) Cells can navigate through a combination of attractive and repulsive gradients with different diffusion radii. (d) Dynamic expression or morphogenetic movements may cause a repositioning of the chemotactic field, causing the cells to respond to the changing location of the chemotactic factor. (e) Correct migration may be achieved by the combination of a chemotactic factor (blue gradient) and a permissive (green) or repulsive (red) substrate. Cells move towards the source (S) of the chemotactic gradient but their migration path and final position are governed by the substrate. See text for examples.

Figure 3.

Border cell migration during Drosophila oogenesis. Border cells (green) arise from the follicular epithelium of the egg chamber and migrate together with the two anterior polar cells (purple) towards the oocyte. On arrival at the oocyte, they turn dorsally to eventually reside at the oocyte nucleus. Migratory guidance cues are provided by ligands for either the PV receptor (blue arrow) or the EGF receptor (red arrow).

Figure 4.

Migration of the PLL primordium and neuromast deposition in zebrafish. (a) The PLL primordium arises near the otic vesicle and migrates towards the tail on a path expressing the chemotactic factor SDF‐1 (blue dotted line). (b) The direction of migration is probably controlled by an intrinsic self‐propagating polarisation mechanism in the primordium that concentrates the expression and activity of the SDF‐1 receptor CXCR4 to the most posterior cells in the primordium (yellow). Deposition of neuromasts along the track of the primordium involves a reduction in speed of the trailing edge at predefined places.

Figure 5.

NC cell migration in Xenopus. (a) NC and placodal cells at the beginning of migration (Nieuwkoop stage 19). The secreted CXCL12 chemotactic gradient causes the NC cells to chase the placodes. On contact between NC cells and placodes, the latter undergo CIL, causing them to run away from the NC. This relocalises the CXCL12 gradient, reinitiating the chase by NC cells. (b) NC cell migration at later stages (stage 22). Positive guidance cues (e.g. CXCL12) and CIL allow directional migration, whereas permissive/restrictive ECM, ephrins and semaphorin‐3 determine the migration routes.

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Further Reading

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Pegoraro C and Monsoro‐Burq AH (2013) Signaling and transcriptional regulation in neural crest specification and migration: Lessons from xenopus embryos. Wiley Interdisciplinary Reviews: Developmental Biology 2: 247–259.

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Van Nieuwenhuysen, Tom, and Vleminckx, Kris(Mar 2014) Cell Migration during Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020864.pub2]