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Modulation of intracellular trafficking regulates cell intercalation in the Drosophila trachea

Nature Cell Biology volume 10, pages 964–970 (2008)Cite this article

Abstract

Through intercalation, a fundamental mechanism underlying elongation during morphogenesis, epithelial cells exchange places in a spatially oriented manner1. Epithelial cells are tightly coupled through distinct intercellular junctions, including adherens junctions. Whether trafficking-mediated regulation of adhesion through adherens junctions modulates intercalation in vivo remains controversial1,2. In Drosophila melanogaster, cells in most branches intercalate during tracheal development. However, Wingless (Wg)-promoted expression of the transcription factor Spalt (Sal) in the dorsal trunk inhibits intercalation3 by an unknown mechanism. Here we have examined the role of trafficking in tracheal intercalation and show that it requires endocytosis, whereas it is opposed by Rab11-mediated recycling in the dorsal trunk. Subapical Rab11 accumulation is enhanced by sal and elevated Rab11-mediated recycling occurs in the dorsal trunk, suggesting that upregulation of Rab11 is one way in which sal inhibits intercalation. We found that dRip11, which regulates Rab11 localization and function4, is regulated by sal and can modulate intercalation. Finally, we provide evidence that levels of E-cadherin (DE-cad), an adherens junction component5 and Rab11-compartment cargo6,7,8, are dynamically regulated by trafficking during tracheal development, and that such regulation modulates intercalation. Our work suggests a mechanism by which trafficking of adhesion molecules regulates intercalation, and shows how this mechanism can be modulated in vivo to influence cell behaviour.

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Figure 1: Relevant background information.
Figure 2: Trafficking and intercalation.
Figure 3: Rab11FIPs in the trachea.
Figure 4: DE-cad and intercalation in the trachea.
Figure 5: Model of trafficking-mediated modulation of intercalation during tracheal development.

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Acknowledgements

We are grateful to many colleagues for sharing reagents. In particular, we thank R. Cohen, S. Eaton, M. González-Gaitán, D. Ready and W. Sullivan for those we used here. We thank S. Araújo, A. Casali, M. Furriols, L. Gervais, I. Greenwald, A. Letizia, E. Martín-Blanco, G. Struhl and J. P. Vincent for comments on the manuscript; N. Martín and R. Méndez for technical assistance; L. Bardia and M. Pons for assistance with confocal microscopy. D.D.S was supported by a Damon Runyon Cancer Research Foundation postdoctoral fellowship (DRG#1840-04). This work was supported by independent grants from the Ministerio de Educación y Ciencia and the Generalitat de Catalunya to J.C. and M.L.

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  1. Daniel D. Shaye

    Present address: Present address: Howard Hughes Medical Institute, 701 W. 168th Street, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,

Authors and Affiliations

  1. Institut de Biologia Molecular de Barcelona-CSIC, C/Baldiri Reixac 10, Barcelona, 08028, Spain

    Daniel D. Shaye, Jordi Casanova & Marta Llimargas

  2. Institut de Recerca Biomèdica de Barcelona, C/Baldiri Reixac 10, Barcelona, 08028, Spain

    Daniel D. Shaye & Jordi Casanova

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Correspondence to Jordi Casanova or Marta Llimargas.

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Supplementary Figures S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, Supplementary Tables S1, S2, S3 and Supplementary Methods (PDF 6681 kb)

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Shaye, D., Casanova, J. & Llimargas, M. Modulation of intracellular trafficking regulates cell intercalation in the Drosophila trachea. Nat Cell Biol 10, 964–970 (2008). https://doi.org/10.1038/ncb1756

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