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Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation

Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA

Convergent extension of the mesoderm is the major driving force of vertebrate gastrulation. During this process, mesodermal cells move toward the future dorsal side of the embryo, then radically change behavior as they initiate extension of the body axis. How cells make this transition in behavior is unknown. We have identified the scaffolding protein and tumor suppressor Gravin as a key regulator of this process in zebrafish embryos. We show that Gravin is required for the conversion of mesodermal cells from a highly migratory behavior to the medio-laterally intercalative behavior required for body axis extension. In the absence of Gravin, paraxial mesodermal cells fail to shut down the protrusive activity mediated by the Rho/ROCK/Myosin II pathway, resulting in embryos with severe extension defects. We propose that Gravin functions as an essential scaffold for regulatory proteins that suppress the migratory behavior of the mesoderm during gastrulation, and suggest that this function also explains how Gravin inhibits invasive behaviors in metastatic cells.

[Keywords: AKAP; convergence and extension; gastrulation; Gravin; Rho; zebrafish]

Received January 24, 2007; revised version accepted May 2, 2007.

² Corresponding author.

E-MAIL kimelman{at}u.washington.edu; FAX (206) 616-8676.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1535007

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