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Group choreography: mechanisms orchestrating the collective movement of border cells

Nature Reviews Molecular Cell Biology volume 13, pages 631–645 (2012)Cite this article

Subjects

Key Points

  • Cell movement is essential for animal development, homeostasis and disease progression. Some cells move in groups, others as single cells.

  • Individual cell migration can be described by a series of reiterated steps: extension of protrusions towards a chemoattractant, adhesion to a substrate, contraction and detachment at the rear. However, cells migrating in complex environments and/or coordinating their movements with other cells require additional regulation.

  • The Drosophila melanogaster border cells have emerged as an excellent model for the study of the coordinated movement of cells in a cohort in vivo. Innovative genetic, live imaging and photomanipulation techniques are providing new insights into the signals governing collective cell migration.

  • Key molecules regulating border cell migration include: the JAK–STAT (Janus kinase–signal transducer and activator of transcription) pathway for selecting the motile cells; the steroid hormone ecdysone for coordinating the timing of movement; and receptor tyrosine kinases and their ligands for providing spatial cues.

  • Unlike individually migrating cells that only adopt a leading–lagging edge polarity, the border cells require two additional axes of polarity for coordinated movement: apical–basal and inside–outside. Because border cells remain in a cluster as they move, they must maintain high levels of adhesion complexes between cells, while dynamically regulating adhesions at the outer edges.

  • Regulators of actin dynamics, such as the Rho.family of GTPases and actin-binding proteins, control much of the mechanics of cell movement. However, the precise roles for specific actin regulators depend on their cellular contexts.

Abstract

Cell movements are essential for animal development and homeostasis but also contribute to disease. Moving cells typically extend protrusions towards a chemoattractant, adhere to the substrate, contract and detach at the rear. It is less clear how cells that migrate in interconnected groups in vivo coordinate their behaviour and navigate through natural environments. The border cells of the Drosophila melanogaster ovary have emerged as an excellent model for the study of collective cell movement, aided by innovative genetic, live imaging, and photomanipulation techniques. Here we provide an overview of the molecular choreography of border cells and its more general implications.

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Figure 1: Drosophila melanogaster oogenesis.
Figure 2: Converging signalling pathways regulate border cell migration.
Figure 3: Migrating border cells are polarized along three axes of polarity.

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Acknowledgements

M. S. G. is funded by a Basil O'Connor Starter Scholar Award from the March of Dimes and a CAREER Award (1054422) from the National Science Foundation. D. J. M. is supported by R01GM46425 and R01GM73164 from the National Institutes of General Medical Sciences. The authors would like to thank current and previous members of the Montell laboratory for providing the images in Figure 1 (Image in figure 1b is courtesy of Ho Lam Tang, image in part b is courtesy of Yu Chiuan Chang, image in part d is courtesy of Mohit Prasad and image in part f is courtesy of Anna Jang).

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Author notes

  1. Michelle Starz-Gaiano

    Present address: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, 21250, Maryland, USA

  2. Wan Hee Yoon

    Present address: Present address: Program in Developmental Biology, Department of Molecular and Human Genetics, Department of Neuroscience, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.,

Authors and Affiliations

  1. Department of Biological Chemistry, Center for Cell Dynamics, The Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Denise J. Montell & Wan Hee Yoon

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Supplementary information

Supplementary information S1 | Time lapse imaging of normal border cell migration.

Nuclear DsRed and cytoplasmic GFP are expressed in the outer, migratory border cells as well as a few anterior (left) and posterior (right) follicle cells that remain in the epithelium. Border cells migrate about 150 micrometres to the oocyte (which contains autofluorescent speckles) and then turn and migrate a few micrometres towards the dorsal side (top). (MOV 4418 kb)

Supplementary information S2 | Polar cell behavior during normal border cell migration

GFP is expressed in a pair of cells at the anterior (left) and posterior (right) poles of the egg chamber. The oocyte is also brightly autofluorescent. Anterior polar cells are carried passively by the migrating border cells. During the movie, polar cells roll as the cluster migrates. (MOV 6860 kb)

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Glossary

Border cells

Six to eight somatic ovarian cells that originate in the follicle epithelium, then coalesce around the polar cells, detach and migrate collectively between germline cells to the border of the oocyte, where they are required for patterning and egg fertilization.

Polar cells

Two somatic follicle cells that are specified at each end of the developing egg chamber. Anterior polar cells secrete signals that specify neighbouring cells to become border cells.

Nurse cells

Auxiliary germline cells that supply the oocyte with synthesized mRNAs, proteins and organelles during insect oogenesis.

Basal lamina

A thin sheet of laminin, collagen IV and proteoglycans that underlies the basal surface of an epithelium.

Ecdysone

The single Drosophila melanogaster steroid hormone, which activates a nuclear hormone receptor complex and initiates transcriptional regulation.

RAC

A 21 kDa GTPase of the RHO-family that is activated by chemoattractants and in turn stimulates polymerization of branched actin networks, resulting in lamellipodial protrusion.

Epithelial to mesenchymal transition

(EMT). A morphological change that is characteristic of some developing tissues and certain forms of cancer. During EMT, cells lose intercellular junctions and apical–basal polarity, become migratory and, in the case of cancer, become invasive.

Filopodia

Thin, dynamic, cellular extensions that contain actin filaments. They are aligned in parallel with their barbed ends pointing towards the tip and are often found in growth cones and at the leading edge of migrating cells.

Lamellipodia

Broad, flat protrusions at the leading edge of a moving cell that are enriched with a branched network of elongating actin filaments, which generate the force to push the cell membrane forward.

Stress fibres

Consist of contractile actin filament bundles that are typically anchored at one or both ends to the extracellular matrix via focal adhesions.

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Montell, D., Yoon, W. & Starz-Gaiano, M. Group choreography: mechanisms orchestrating the collective movement of border cells. Nat Rev Mol Cell Biol 13, 631–645 (2012). https://doi.org/10.1038/nrm3433

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