Segmental Assembly of Fibronectin Matrix Requires rap1b and integrin α5

Authors

  • Simone Lackner,

    1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut
    Current affiliation:
    1. Vision to Action Laboratory, Champalimaud Neuroscience Programme at the Champalimaud Centre for the Unknown, Lisbon, Portugal
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    • Simone Lackner and Jamie Schwendinger-Schreck contributed equally to this article.

  • Jamie Schwendinger-Schreck,

    1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut
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    • Simone Lackner and Jamie Schwendinger-Schreck contributed equally to this article.

  • Dörthe Jülich,

    1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut
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  • Scott A. Holley

    Corresponding author
    • Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut
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Correspondence to: Scott Holley, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511. E-mail: scott.holley@yale.edu

Abstract

Background: During segmentation of the zebrafish embryo, inside-out signaling activates Integrin α5, which is necessary for somite border morphogenesis. The direct activator of Integrin α5 during this process is unknown. One candidate is Rap1b, a small monomeric GTPase implicated in Integrin activation in the immune system. Results: Knockdown of rap1b, or overexpression of a dominant negative rap1b, causes a mild axis elongation defect in zebrafish. However, disruption of rap1b function in integrin α5−/− mutants results in a strong reduction in Fibronectin (FN) matrix assembly in the paraxial mesoderm and a failure in somite border morphogenesis along the entire anterior-posterior axis. Somite patterning appears unaffected, as her1 oscillations are maintained in single and double morphants/mutants, but somite polarity is gradually lost in itgα5−/−; rap1b MO embryos. Conclusions: In itgα5/ mutants, rap1b is required for proper somite border morphogenesis in zebrafish. The loss of somite borders is not a result of aberrant segmental patterning. Rather, somite boundary formation initiates but is not completed, due to the failure to assemble FN matrix along the nascent boundary. We propose a model in which Rap1b activates Integrin/Fibronectin receptors as part of an “inside-out” signaling pathway that promotes Integrin binding to FN, FN matrix assembly, and subsequent stabilization of morphological somite boundaries. Developmental Dynamics 242:122–131, 2013. © 2012 Wiley Periodicals, Inc.

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