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Cytoskeletal polarity mediates localized induction of the heart progenitor lineage

Cooley, James and Whitaker, Stacia and Sweeney, Sarah and Fraser, Scott and Davidson, Brad (2011) Cytoskeletal polarity mediates localized induction of the heart progenitor lineage. Nature Cell Biology, 13 (8). pp. 952-957. ISSN 1465-7392.

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Cells must make appropriate fate decisions within a complex and dynamic environment. In vitro studies indicate that the cytoskeleton acts as an integrative platform for this environmental input. External signals regulate cytoskeletal dynamics and the cytoskeleton reciprocally modulates signal transduction. However, in vivo studies linking cytoskeleton/signalling interactions to embryonic cell fate specification remain limited. 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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Fraser, Scott0000-0002-5377-0223
Additional Information:© 2011 Macmillan Publishers Limited. Received 3 June 2010; accepted 6 June 2011; published online 24 July 2011. 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. Author 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.
Funding AgencyGrant Number
American Heart Association (AHA)0730345N
American Recovery and Reinvestment Act (ARRA)3R01HL091027-01A1S1
Science Foundation of ArizonaUNSPECIFIED
Issue or Number:8
Record Number:CaltechAUTHORS:20110823-102824466
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24996
Deposited By: Jason Perez
Deposited On:23 Aug 2011 20:26
Last Modified:03 Oct 2019 03:01

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