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Border-cell migration: the race is on

Nature Reviews Molecular Cell Biology volume 4, pages 13–24 (2003)Cite this article

Abstract

The conversion of stationary epithelial cells into migratory, invasive cells is important for normal embryonic development and tumour metastasis. Border-cell migration in the ovary of Drosophila melanogaster has emerged as a simple, genetically tractable model for studying this process. Three distinct signals, which are also upregulated in cancer, control border-cell migration, so identifying further genes that are involved in border-cell migration could provide new insights into tumour invasion.

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Figure 1: Schematic drawing of an egg chamber.
Figure 2: Border-cell migration in wild-type and slbo egg chambers.
Figure 3: Expression of Jak–Stat pathway components during border-cell migration.
Figure 4: Function of Jak–Stat signalling in border-cell migration.
Figure 5: Expression patterns of Pvf and Pvr.
Figure 6: Guidance of border-cell migration by Pvf at stage 9.
Figure 7: Signals governing border-cell migration.

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References

  1. Bai, J., Uehara, Y. & Montell, D. J. Regulation of invasive cell behavior by Taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell 103, 1047–1058 (2000). This paper reports the surprising finding that Ecdysone, signalling through the Ecdysone receptor and its coactivator Taiman, regulates border-cell migration.

    Article  CAS  PubMed  Google Scholar 

  2. Silver, D. L. & Montell, D. J. Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila. Cell 107, 831–841 (2001). This paper reports the identification of the signal and signalling pathway that distinguishes the cells that acquire the ability to migrate from those that cannot.

    Article  CAS  PubMed  Google Scholar 

  3. Duchek, P., Somogyi, K., Jekely, G., Beccari, S. & Rørth, P. Guidance of cell migration by the Drosophila pdgf/vegf receptor. Cell 107, 17–26 (2001). This paper reports the identification of a growth factor expressed in the germline, which acts through a receptor tyrosine kinase expressed by all of the follicle cells and which is involved in guiding the border cells to the oocyte.

    Article  CAS  PubMed  Google Scholar 

  4. King, R. C. Ovarian Development in Drosophila melanogaster (Academic, New York, 1970).

    Google Scholar 

  5. Spradling, A. C. in The Development of Drosophila melanogaster (eds Bate, M. & Martinez-Arias, A.) 1–70 (Cold Spring Harbor Laboratory Press, New York, 1993).

    Google Scholar 

  6. Margolis, J. & Spradling, A. C. Identification and behavior of epithelial stem cells in the Drosophila ovary. Development 121, 3797–3807 (1995).

    CAS  PubMed  Google Scholar 

  7. Montell, D. J., Rørth, P. & Spradling, A. C. slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP. Cell 71, 51–62 (1992). This paper reports the identification of the first mutation showing border-cell migration defects and the cloning of the corresponding gene.

    Article  CAS  PubMed  Google Scholar 

  8. Savant-Bhonsale, S. & Montell, D. J. torso-like encodes the localized determinant of Drosophila terminal pattern formation. Genes Dev. 7, 2548–2555 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Rørth, P. & Montell, D. J. Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development. Genes Dev. 6, 2299–2311 (1992).

    Article  PubMed  Google Scholar 

  10. Oda, H., Uemura, T. & Takeichi, M. Phenotypic analysis of null mutants for DE-cadherin and Armadillo in Drosophila ovaries reveals distinct aspects of their functions in cell adhesion and cytoskeletal organization. Genes Cells 2, 29–40 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Niewiadomska, P., Godt, D. & Tepass, U. DE-cadherin is required for intercellular motility during Drosophila oogenesis. J. Cell Biol. 144, 533–547 (1999). This work reports the finding that DE-cadherin is required both in border cells and in nurse cells for border-cell migration to occur.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Takeichi, M. Cadherins in cancer: implications for invasion and metastasis. Curr. Opin. Cell Biol. 5, 806–811 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. Fujita, Y. et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nature Cell Biol. 4, 222–231 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Sundfeldt, K. et al. E-cadherin expression in human epithelial ovarian cancer and normal ovary. Int. J. Cancer 74, 275–280 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Kim, J. B. et al. N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility. J. Cell Biol. 151, 1193–1206 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lilien, J., Balsamo, J., Arregui, C. & Xu, G. Turn-off, drop-out: functional state switching of cadherins. Dev. Dyn. 224, 18–29 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Liu, Y. & Montell, D. J. jing: a downstream target of slbo required for developmental control of border cell migration. Development 128, 321–330 (2001).

    CAS  PubMed  Google Scholar 

  18. Geisbrecht, E. R. & Montell, D. J. Myosin VI is required for E-cadherin-mediated border cell migration. Nature Cell Biol. 4, 616–620 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Liu, Y. & Montell, D. J. Identification of mutations that cause cell migration defects in mosaic clones. Development 126, 1869–1878 (1999).

    CAS  PubMed  Google Scholar 

  20. Rørth, P. et al. Systematic gain-of-function genetics in Drosophila. Development 125, 1049–1057 (1998).

    PubMed  Google Scholar 

  21. Han, D. D., Stein, D. & Stevens, L. M. Investigating the function of follicular subpopulations during Drosophila oogenesis through hormone-dependent enhancer-targeted cell ablation. Development 127, 573–583 (2000).

    CAS  PubMed  Google Scholar 

  22. Aaronson, D. S. & Horvath, C. M. A road map for those who don't know JAK–STAT. Science 296, 1653–1655 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Harrison, D. A., McCoon, P. E., Binari, R., Gilman, M. & Perrimon, N. Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. Genes Dev. 12, 3252–3263 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Beccari, S., Teixeira, L. & Rørth, P. The JAK/STAT pathway is required for border cell migration during Drosophila oogenesis. Mech. Dev. 111, 115–123 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. LaBonne, C. & Bronner-Fraser, M. Snail-related transcriptional repressors are required in Xenopus for both the induction of the neural crest and its subsequent migration. Dev. Biol. 221, 195–205 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Yamashita, S. et al. Stat3 controls cell movements during zebrafish gastrulation. Dev. Cell 2, 363–375 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Sano, S. et al. Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J. 18, 4657–4668 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bromberg, J. & Darnell, J. E. Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19, 2468–2473 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Buettner, R., Mora, L. B. & Jove, R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin. Cancer Res. 8, 945–954 (2002).

    CAS  PubMed  Google Scholar 

  30. Anzick, S. L. et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965–968 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Chen, J. D. Steroid/nuclear receptor coactivators. Vitam. Horm. 58, 391–448 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Fisher, B. et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl Cancer Inst. 90, 1371–1388 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Riddiford, L. M. in The Development of Drosophila melanogaster (eds Bate, M. & Martinez Arias, A.) 899–940 (Cold Spring Harbor Laboratory Press, New York, 1993).

    Google Scholar 

  34. Su, M. et al. Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Development 127, 585–594 (2000).

    CAS  PubMed  Google Scholar 

  35. Yu, T. W. & Bargmann, C. I. Dynamic regulation of axon guidance. Nature Neurosci. 4, 1169–1176 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Hedgecock, E. M., Culotti, J. G. & Hall, D. H. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4, 61–85 (1990).

    Article  CAS  PubMed  Google Scholar 

  37. DeVore, D. L., Horvitz, H. R. & Stern, M. J. An FGF receptor signaling pathway is required for the normal cell migrations of the sex myoblasts in C. elegans hermaphrodites. Cell 83, 611–620 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Simpson, J. H., Bland, K. S., Fetter, R. D. & Goodman, C. S. Short-range and long-range guidance by Slit and its Robo receptors: a combinatorial code of Robo receptors controls lateral position. Cell 103, 1019–1032 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Heino, T. I. et al. The Drosophila VEGF receptor homolog is expressed in hemocytes. Mech. Dev. 109, 69–77 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Cho, N. K. et al. Developmental control of blood cell migration by the Drosophila VEGF pathway. Cell 108, 865–876 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Duchek, P. & Rørth, P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science 291, 131–133 (2001). This paper shows that signalling through the Egf receptor controls the late, dorsalward migration of the border cells.

    Article  CAS  PubMed  Google Scholar 

  42. Wasserman, J. D. & Freeman, M. An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95, 355–364 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Carl, T. F., Dufton, C., Hanken, J. & Klymkowsky, M. W. Inhibition of neural crest migration in Xenopus using antisense slug RNA. Dev. Biol. 213, 101–115 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. O'Rourke, M. P. & Tam, P. P. Twist functions in mouse development. Int. J. Dev. Biol. 46, 401–413 (2002).

    CAS  PubMed  Google Scholar 

  45. Gomperts, M., Garcia-Castro, M., Wylie, C. & Heasman, J. Interactions between primordial germ cells play a role in their migration in mouse embryos. Development 120, 135–141 (1994).

    CAS  PubMed  Google Scholar 

  46. Kulesa, P. M. & Fraser, S. E. In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches. Development 127, 1161–1172 (2000).

    CAS  PubMed  Google Scholar 

  47. Alexandre, D. & Ghysen, A. Somatotopy of the lateral line projection in larval zebrafish. Proc. Natl Acad. Sci. USA 96, 7558–7562 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nabeshima, K., Inoue, T., Shimao, Y., Kataoka, H. & Koono, M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol. Histopathol. 14, 1183–1197 (1999).

    CAS  PubMed  Google Scholar 

  49. Liu, H., Chen, B., Zardi, L. & Ramos, D. M. Soluble fibronectin promotes migration of oral squamous-cell carcinoma cells. Int. J. Cancer 78, 261–267 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Xie, T. & Spradling, A. C. A niche maintaining germ line stem cells in the Drosophila ovary. Science 290, 328–330 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Xu, T. & Harrison, S. D. Mosaic analysis using FLP recombinase. Methods Cell Biol. 44, 655–681 (1994).

    Article  CAS  PubMed  Google Scholar 

  52. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  PubMed  Google Scholar 

  53. Tanentzapf, G., Smith, C., McGlade, J. & Tepass, U. Apical, lateral, and basal polarization cues contribute to the development of the follicular epithelium during Drosophila oogenesis. J. Cell Biol. 151, 891–904 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fulga, T. A. & Rørth, P. Invasive cell migration is initiated by guided growth of long cellular extensions. Nature Cell Biol. 4, 715–719 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Murphy, A. M. & Montell, D. J. Cell type-specific roles for Cdc42, Rac, and RhoL in Drosophila oogenesis. J. Cell Biol. 133, 617–630 (1996).

    Article  CAS  PubMed  Google Scholar 

  56. Rørth, P., Szabo, K. & Texido, G. The level of C/EBP protein is critical for cell migration during Drosophila oogenesis and is tightly controlled by regulated degradation. Mol. Cell 6, 23–30 (2000).

    Article  PubMed  Google Scholar 

  57. Edwards, K. A. & Kiehart, D. P. Drosophila nonmuscle myosin II has multiple essential roles in imaginal disc and egg chamber morphogenesis. Development. 122, 1499–1511 (1996).

    CAS  PubMed  Google Scholar 

  58. Oro, A. E., McKeown, M. & Evans, R. M. The Drosophila retinoid X receptor homolog ultraspiracle functions in both female reproduction and eye morphogenesis. Development 115, 449–462 (1992).

    CAS  PubMed  Google Scholar 

  59. Henrich, V. C., Tucker, R. L., Maroni, G. & Gilbert, L. I. The ecdysoneless (ecd1ts) mutation disrupts ecdysteroid synthesis autonomously in the ring gland of Drosophila melanogaster. Dev. Biol. 120, 50–55 (1987).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The author would like to thank all the members of her laboratory for critical reading of the manuscript and their contributions to the work that is described.

Author information

Authors and Affiliations

  1. Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, 21205-2185, Maryland, USA

    Denise J. Montell

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  1. Denise J. Montell
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Related links

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DATABASES

InterPro

SH2

FlyBase

slbo

tai

tsl

upd

vein

LocusLink

C/EBP

Swiss-Prot

AIB1

DE-cadherin

Domeless

EcR

Grk

Hopscotch

Jing

myosin VI

Pvf1

Pvf2

Pvf3

Slug

Spitz

Stat3

Stat92e

Usp

WormBase

daf-12

unc-5

FURTHER INFORMATION

Denise Montell's laboratory

Cell Migration Consortium

Glossary

NURSE CELL

An auxiliary cell that supplies the oocyte with synthesized messenger RNAs and proteins during insect oogenesis.

POLYPLOID CELL

A cell that has three or more times the haploid number of chromosomes in its nucleus.

HAEMOLYMPH

A fluid that is present in the second body cavity of some invertebrates. It is considered to be functionally equivalent to the blood and lymph of higher organisms.

P-ELEMENT

A transposable element from Drosophila melanogaster that has been extremely useful both as an insertional mutagen and as a vector for generating transgenic animals.

POINTED END

This is defined by the arrowhead appearance of myosin head fragments that are bound to the actin filaments.

CELL AUTONOMY

A gene is said to act cell autonomously if the cell that shows the mutant phenotype is the cell in which that gene functions. Most genes act cell autonomously. Conversely, a gene acts non-automonously if expression of the gene in one cell influences the phenotype of a different cell.

SRC-HOMOLOGY-2 DOMAIN

(SH2 domain). A protein motif that recognizes and binds tyrosine-phosphorylated sequences, and thereby has a key role in relaying cascades of signal transduction.

NULL ALLELE

A mutation that completely eliminates the function of a gene.

DOMINANT-NEGATIVE

A defective protein that retains its interaction abilities and so distorts or competes with normal proteins.

HYPOMORPHIC ALLELE

A mutation that reduces but does not eliminate the function of a gene.

NEURAL CREST

A group of embryonic cells that separate from the embryonic neural plate and migrate, giving rise to the spinal and autonomic ganglia, peripheral glia, chromaffin cells, melanocytes and some haematopoietic cells.

KERATINOCYTE

A differentiated epithelial cell of the skin.

PENETRANT

A phenotype that is completely penetrant is equally strong in every cell that is homozygous for the mutation. Conversely, an incompletely penetrant phenotype is manifest in some mutant cells, or individuals, but is not obvious in others.

ADHERENS JUNCTION

A cell–cell adhesion complex that is composed of cadherins and catenins that are attached to cytoplasmic actin filaments.

SEPTATE JUNCTION

A junction basal to the zonula adherens in Drosophila epithelial cells. It is thought to function similarly to the tight junction in vertebrate cells.

GAP JUNCTION

A communicating junction (permeant to molecules up to 1 kDa) between adjacent cells, which is composed of 12 connexin protein subunits, six of which form a connexon or hemichannel that is contributed by each of the coupled cells.

DELAMINATE

To emerge from an epithelial layer.

RNA INTERFERENCE

(RNAi). The process by which an introduced double-stranded RNA silences specifically the expression of genes through degradation of their cognate messenger RNAs.

PRIMORDIUM

An organ or part at the earliest stage of its development; a rudiment.

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Montell, D. Border-cell migration: the race is on. Nat Rev Mol Cell Biol 4, 13–24 (2003). https://doi.org/10.1038/nrm1006

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