Letter | Published:

Cytoskeletal polarity mediates localized induction of the heart progenitor lineage

Nature Cell Biology volume 13, pages 952957 (2011) | Download Citation

Abstract

Cells must make appropriate fate decisions within a complex and dynamic environment1. In vitro studies indicate that the cytoskeleton acts as an integrative platform for this environmental input2. External signals regulate cytoskeletal dynamics and the cytoskeleton reciprocally modulates signal transduction3,4. However, in vivo studies linking cytoskeleton/signalling interactions to embryonic cell fate specification remain limited5,6,7. Here we show that the cytoskeleton modulates heart progenitor cell fate. Our studies focus on differential induction of heart fate in the basal chordate Ciona intestinalis. We have found that differential induction does not simply reflect differential exposure to the inductive signal. Instead, pre-cardiac cells employ polarized, invasive protrusions to localize their response to an ungraded signal. Through targeted manipulation of the cytoskeletal regulator CDC42, we are able to depolarize protrusive activity and generate uniform heart progenitor fate specification. Furthermore, we are able to restore differential induction by repolarizing protrusive activity. These findings illustrate how bi-directional interactions between intercellular signalling and the cytoskeleton can influence embryonic development. In particular, these studies highlight the potential for dynamic cytoskeletal changes to refine cell fate specification in response to crude signal gradients.

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Acknowledgements

The ensconsin–GFP construct was generously provided by F. Robin (University of Chicago, USA), the CDC42 constructs by L. Christiaen (New York University, USA), the GPI–GFP construct by A. Gregorio (Weill Medical College of Cornell University, USA) and K. Hadjantonakis (Sloan-Kettering Institute, USA) and the FRET biosensor constructs by M. Matsuda (Osaka University, Japan) and D. Kamiyama (University of Miami, USA); the Rho constructs were designed and tested by J. Norton (University of Arizona). We would also like to thank G. Rogers and D. Buster for their advice and assistance on antibody production, M. Salanga for guidance on FRET imaging, T. Warholac for assistance with statistical analysis and M. Barnet for use of his cooling system for live-embryo imaging. We thank D. Sherwood, H. Granzier, A. Wikramanayake and the members of the U. A. Molecular Cardiovascular Research Program for their input and critical evaluation of the manuscript. Live-embryo imaging was carried out in the facilities of the Biological Imaging Center, under support from the Caltech Beckman Institute and the Beckman Foundation. The work was supported by grants to B.D. from the AHA (0730345N) and NIH (R01HL091027) along with supplemental funding from the American Recovery Act to support J.C. (3R01HL091027-01A1S1) and support for S.W. from the Science Foundation of Arizona.

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Affiliations

  1. Department of Molecular and Cellular Biology, Molecular Cardiovascular Research Program, University of Arizona, Arizona 85724, USA

    • James Cooley
    • , Stacia Whitaker
    • , Sarah Sweeney
    •  & Brad Davidson
  2. Department of Biology, Imaging Center, Beckman Institute, California Institute of Technology, California 91125, USA

    • Sarah Sweeney
    •  & Scott Fraser

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Contributions

J.C., S.W. and B.D. designed the project and carried out most of the experiments including data analysis. S.F. provided material and technical support for live-cell imaging carried out by S.S., J.C. and B.D. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Brad Davidson.

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DOI

https://doi.org/10.1038/ncb2291

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