Skip to main content
SpringerLink
Log in

Developmental regulation of cell migration

Insights from a genetic approach in drosophila

  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Cell movements are fascinating and dramatic features of normal animal development. Moreover, failures in cell migration can lead to birth defects, and inappropriate cell migration can lead to cancer metastasis. Genetic approaches are beginning to provide some insights into the molecular basis for the developmental regulation of cell migration. This review discusses the progress that has been made in understanding the regulation of cell migration duringDrosophila development, using a molecular genetic approach. In particular, these studies have implicated signaling through a receptor tyrosine kinase in the spatial control of migration. Reorganization of the cytoskeleton, under the control of the guanosine triphosphatase, Rac, is also critical for cell migration. Finally, genetic studies have demonstrated that the timing of cell migration is under transcriptional control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lauffenburger, D. A. and Horwitz, A. F. (1996) Cell migration: a physically integrated molecular process.Cell 84, 359–369.

    Article  PubMed  CAS  Google Scholar 

  2. Chen, M. Y., Insall, R. H., and Devreotes, P. N. (1996) Signaling through chemoattractant receptors inDictyostelium.Trends Genet. 12, 52–57.

    Article  PubMed  CAS  Google Scholar 

  3. Hedgecock, E. M. (1987) Genetics of cell and axon migrations inCaenorhabditis elegans.Development 100, 365–382.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Garriga, G. and Stern, M. J. (1994) Hams and Egls: genetic analysis of cell migration inCaenorhabditis elegans.Curr. Opin. Gene. Dev. 4, 575–580.

    Article  CAS  Google Scholar 

  6. Harris, J., Honigberg, L., Robinson, N., and Kenyon, C. (1996) Neuronal cell migration inC. elegans: regulation of Hox gene expression and cell position.Development 122, 3117–3131.

    PubMed  CAS  Google Scholar 

  7. Wightman, B., Clark, S. G., Taskar, A. M., Forrester, W. C., Maricq, A. V., Bargmann, C. I., and Garriga, G. (1996) TheC. elegans gene vab-8 guides posteriorly directed axon outgrowth and cell migration.Development 122, 671–682.

    PubMed  CAS  Google Scholar 

  8. Howard, K., Jaglarz, M., Zhang, N., Shah, J., and Warrior, R. (1993) Migration ofDrosophila germ cells: analysis using enhancer trap lines.Development (Suppl), 213–218.

    Google Scholar 

  9. Manning, G. and Krasnow, M. A. (1993) Development of theDrosophila tracheal system, in Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 609–686.

    Google Scholar 

  10. Klambt, C., Jacobs, J. R., and Goodman, C. S. (1991) The midline of theDrosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance.Cell 64, 801–815.

    Article  PubMed  CAS  Google Scholar 

  11. Choi, K. W. and Benzer, S. (1994) Migration of glia along photoreceptor axons in the developingDrosophila eye.Neuron 12, 423–431.

    Article  PubMed  CAS  Google Scholar 

  12. King, R. C. (1970) Ovarian development inDrosophila melanogaster. Academic, New York, NY.

    Google Scholar 

  13. Karpen, G. and Spradling, A. C. (1992) Analysis of subtelomeric heterochromatin in aDrosophila minichromosome Dp1187 by single P-element insertional mutagenesis.Genetics 132, 737–753.

    PubMed  CAS  Google Scholar 

  14. Montell, D. J., Rørth, P., and Spradling, A. C. (1992)slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodesDrosophila C/EBP.Cell 71, 51–62.

    Article  PubMed  CAS  Google Scholar 

  15. Birkenmeier, E. H., Gwynn, B. G., Howard, S., Herry, J., Gordon, J. I., Landschulz, W. H., and McKnight, S. L. (1989) Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein.Genes Dev.3, 1146–1156.

    Article  PubMed  CAS  Google Scholar 

  16. Cao, Z., Umek, R. M., and McKnight, S. L. (1991) Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.Genes Dev. 5, 1539–1552.

    Article  Google Scholar 

  17. Christy, R. J., Yang, V. W., Ntambi, J. M., Geiman, D. E., Landschultz, W. H., Friedman, A. D., et al. (1989) Differentiation-induced expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes.Genes Dev. 3, 1323–1335.

    Article  PubMed  CAS  Google Scholar 

  18. Lin, F. and Lane, M. D. (1992) Antisense CCAAT/enhancer binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes.Genes Dev. 6, 533–544.

    Article  PubMed  CAS  Google Scholar 

  19. Friedman, A. D., Landschultz, W. H., and McKnight, S. L. (1989) CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells.Genes Dev. 3, 1314–1322.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Wang, N.-d., Finegold, M. J., and Darlington, G. J. (1995) Impaired energy homeostasis in C/EBP knockout mice.Science 269, 1108–1111.

    Article  PubMed  CAS  Google Scholar 

  22. Donovan, P., Stott, D., Cairns, A. L., Heasman, J., and Wylie, C. C. (1986) Migratory and postmigratory mouse primordial germ cells behave differently in culture.Cell 44, 831–838.

    Article  PubMed  CAS  Google Scholar 

  23. Glazer, L. and Shilo, B.-Z. (1991) TheDrosophila FGF receptor homolog is expressed in the embryonic trachael system and appears to be required for directed trachael cell extension.Genes Dev. 5, 697–705.

    Article  PubMed  CAS  Google Scholar 

  24. Klambt, C., Glazer, L., and Shilo, B. Z. (1992)Breathless, aDrosophila FGF receptor homolog, is essential for migration of trachael and specific midline glial cells.Genes Dev. 6, 1668–1678.

    Article  PubMed  CAS  Google Scholar 

  25. Kundra, V., Escobedo, J. A., Kazlauskas, A., Kim, H. K., Rhee, S. G., Williams, L. T., and Zetter, B. R. (1994) Regulation of chemotaxis by the platelet-derived growth factor receptorbeta.Nature 367, 474–476.

    Article  PubMed  CAS  Google Scholar 

  26. Kundra, V., Soker, S., and Zetter, B. R. (1994) Excess early signaling activity inhibits cellular chemotaxis toward PDGF-BB.Oncogene 9, 1429–1435.

    PubMed  CAS  Google Scholar 

  27. Post, P. L., DeBiasio, R. L., and Taylor, D. L. (1995) A fluorescent protein biosensor of myosin II regulatory light chain phosphorylation reports a gradient of phosphorylated myosin II in migrating cells.Mol. Biol. Cell 6, 1755–1768.

    PubMed  CAS  Google Scholar 

  28. Lee, T., Hacohen, N., Krasnow, M. A., and Montell, D. J. (1996b) Regulated breathless receptor tyrosine kinase activity required to pattern cell migration and branching in theDrosophila tracheal system.Genes Dev. 10, 2912–2921.

    Article  PubMed  CAS  Google Scholar 

  29. Sutherland, D., Samakovlis, C., and Krasnow, M. A. (1996)branchless encodes aDrosophila fibroblast growth factor homolog that controls tracheal cell migration and branching.Cell 87, 1091–1101.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  31. Ciruna, B. G., Schwartz, L., Harpal, K., Yamaguchi, T. P., and Rossant, J. (1997) Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movemvent through the primitive streak.Development 124, 2829–2841.

    PubMed  CAS  Google Scholar 

  32. Murphy, A. M., Lee, T., Andrews, C. M., Shilo, B. Z., and Montell, D. J. (1995) The Breathless FGF receptor homolog, a downstream target ofDrosophila C/EBP in the developmental control of cell migration.Development 121, 2255–2263.

    PubMed  CAS  Google Scholar 

  33. Barinaga, M. (1995) Receptors find work as guides.Science 269, 1668–1670.

    Article  PubMed  CAS  Google Scholar 

  34. Tessier-Lavigne, M. and Goodman, C. S. (1996) The molecular biology of axon guidance.Science 274, 1123–1132.

    Article  PubMed  CAS  Google Scholar 

  35. Lee, T., Feig, L., and Montell, D. J. (1996a) Two distinct roles for Ras in a developmentally regulated cell migration.Development 122, 409–418.

    PubMed  CAS  Google Scholar 

  36. Luo, L., Liao, Y. J., Jan, L. Y., and Jan, Y. N. (1994) Distinct morphogenetic functions of similar small GTPases:Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.Genes Dev. 8, 1787–1802.

    Article  PubMed  CAS  Google Scholar 

  37. Hariharan, I. K., Hu, K. Q., and Settleman, J. (1995) Characterization of rho GTPase family homologues inDrosophila melanogaster: overexpressing Rho 1 in retinal cells causes a late developmental defect.EMBO J. 14, 292.

    PubMed  CAS  Google Scholar 

  38. Ridley, A. J. and Hall, A. (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.Cell 70, 389–399.

    Article  PubMed  CAS  Google Scholar 

  39. Ridley, A. J., Paterson, H. F., Johnston, C. L., Diekmann, D., and Hall, A. (1992) The small GTP-binding protein Rac regulates growth factor-induced membrane ruffling.Cell 70, 401–410.

    Article  PubMed  CAS  Google Scholar 

  40. Nobes, C. D. and Hall, A. (1995) Rho, Rac and Cdc42 GTPases regulate the assembly of multi-molecular focal complexes associated with actin stress fibers, lamellipodia and filopodia.Cell 81, 53–62.

    Article  PubMed  CAS  Google Scholar 

  41. Murphy, A. M. and Montell, D. J. (1996) Cell Type-specific Roles for Cdc42, Rac, and RhoL inDrosophila oogenesis.J. Cell Biol. 133, 617–630.

    Article  PubMed  CAS  Google Scholar 

  42. Michiels, F., Habets, G. G., Stam, J. C., van der Kammen, R. A., and Collard, J. G. (1995) A role for Rac in Tiam 1-induced membrane ruffling and invasion.Nature 375, 338–340.

    Article  PubMed  CAS  Google Scholar 

  43. Habets, G. G., Scholtes, E. H., Zuydgeest, D., van der Kammen, R. A., Stam, J. C., Berns, A., and Collard, J. G. (1994) Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins.Cell 77, 537–549.

    Article  PubMed  CAS  Google Scholar 

  44. Luo, L., Hensch, T. K., Ackerman, L., Barbel, S., Jan, L. Y., and Jan, Y. N. (1996) Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines.Nature 379, 837–840.

    Article  PubMed  CAS  Google Scholar 

  45. Manstein, D. J., Titus, M. A., De Lozanne, A., and Spudich, J. A. (1989) Gene replacement inDictyostelium: generation of myosin null mutants.EMBO J. 8, 923–932.

    PubMed  CAS  Google Scholar 

  46. Xu, X. S., Kuspa, A., Fuller, D., Loomis, W. F., and Knecht, D. A. (1996) Cell-cell adhesion prevents mutant cells lacking myosin II from penetrating aggregation streams ofDictyostelium.Dev. Biol. 175, 218–226.

    Article  PubMed  CAS  Google Scholar 

  47. Knecht, D. A. and Shelden, E. (1995) Three-dimensional localization of wild-type and myosin II mutant cells during morphogenesis ofDictyostelium.Dev. Biol. 170, 434–444.

    Article  PubMed  CAS  Google Scholar 

  48. Shelden, E. and Knecht, D. A. (1995) Mutants lacking myosin II cannot resist forces generated during multicellular morphogenesis.J. Cell Sci. 108, 1105–1115.

    PubMed  CAS  Google Scholar 

  49. Jay, P. Y., Pham, P. A., Wong, S. A., and Elson, E. L. (1995) A mechanical function of myosin II in cell motility.J. Cell Sci. 108, 387–393.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  51. Karess, R. E., Chang, X. J., Edwards, K. A., Kulkarni, S., Aguilera, I., and Kiehart, D. P. (1991) The regulatory light chain of nonmuscle myosin is encoded by spaghetti-squash, a gene required for cytokinesis inDrosophila.Cell 65, 1177–1189.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Denise J. Montell

Authors
  1. Denise J. Montell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denise J. Montell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montell, D.J. Developmental regulation of cell migration. Cell Biochem Biophys 31, 219–229 (1999). https://doi.org/10.1007/BF02738240

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02738240

Index Entries

Search

Navigation