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Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine–vulval attachment in Caenorhabditis elegans

Nature Cell Biology volume 13, pages 641–651 (2011)Cite this article

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Abstract

Large gaps in basement membrane occur at sites of cell invasion and tissue remodelling in development and cancer. Though never followed directly in vivo, basement membrane dissolution or reduced synthesis have been postulated to create these gaps. Using landmark photobleaching and optical highlighting of laminin and type IV collagen, we find that a new mechanism, basement membrane sliding, underlies basement membrane gap enlargement during uterine–vulval attachment in Caenorhabditis elegans. Laser ablation and mutant analysis reveal that the invaginating vulval cells promote basement membrane movement. Further, an RNA interference and expression screen identifies the integrin INA-1/PAT-3 and VAB-19, homologue of the tumour suppressor Kank, as regulators of basement membrane opening. Both concentrate within vulval cells at the basement membrane gap boundary and halt expansion of the shifting basement membrane. Basement membrane sliding followed by targeted adhesion represents a new mechanism for creating precise basement membrane breaches that can be used by cells to break down compartment boundaries.

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Figure 1: The gap in the basement membrane expands during uterine–vulval attachment.
Figure 2: The role of the uterine cells during basement membrane gap formation.
Figure 3: The VPCs expand the breach in the basement membrane.
Figure 4: Basement membrane sliding underlies basement membrane gap enlargement.
Figure 5: INA-1/PAT-3 (integrin) and VAB-19 (Kank) stabilize the basement membrane gap boundary.
Figure 6: The uterine and vulval cells act together to limit basement membrane gap expansion.

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  • 28 October 2013

    In the version of this Article originally published online, the citation of Nature Protocols at the end of the 'Optical highlighting (photoconversion) of basement membrane components' section in the Methods was incorrect. It has been corrected in all online versions of the Article.

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Acknowledgements

We are grateful to A. Chisholm for the vab-19::GFP vector; J. Culotti for the mig-6(ev700)strain; J. Schwarzbauer for the pat-3 HA– β-tail vector; S. Mitani for the deletion mutant (tm1291), S. Johnson of the Duke University LMCF for imaging advice, the Caenorhabditis Genetic Center for strains, and A. Schindler, D. Matus and L. Lilley for comments on the manuscript. This work was supported by a Basil O’Connor Scholars Research Award, The Pew Scholars Program in the Biomedical Sciences and NIH grants GM079320 and GM079320-03S1 to D.R.S., HD027211 to J.M.K. and a JSPS Postdoctoral Fellow for Research Abroad Award to S.I.

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Authors and Affiliations

  1. Department of Biology, Duke University, Science Drive, Durham, North Carolina 27708, Box 90388, USA

    Shinji Ihara, Elliott J. Hagedorn, Meghan A. Morrissey, Qiuyi Chi & David R. Sherwood

  2. Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA

    Fumio Motegi

  3. Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA

    James M. Kramer

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Contributions

S.I. carried out most of the experiments. All other authors carried out particular subsets of experiments or developed key reagents. D.R.S. and S.I. designed the project and D.R.S., S.I., E.J.H. and M.A.M. wrote the manuscript.

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Correspondence to David R. Sherwood.

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Ihara, S., Hagedorn, E., Morrissey, M. et al. Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine–vulval attachment in Caenorhabditis elegans. Nat Cell Biol 13, 641–651 (2011). https://doi.org/10.1038/ncb2233

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