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Dishevelled controls cell polarity during Xenopus gastrulation


Although cell movements are vital for establishing the normal architecture of embryos, it is unclear how these movements are regulated during development in vertebrates. Inhibition of Xenopus Dishevelled (Xdsh) function disrupts convergent extension movements of cells during gastrulation, but the mechanism of this effect is unclear, as cell fates are not affected1. In Drosophila, Dishevelled controls both cell fate and cell polarity2,3,4, but whether Dishevelled is involved in controlling cell polarity in vertebrate embryos has not been investigated. Here we show, using time-lapse confocal microscopy, that the failure of cells lacking Xdsh function to undergo convergent extension results from defects in cell polarity. Furthermore, Xdsh mutations that inhibit convergent extension correspond to mutations in Drosophila Dishevelled that selectively perturb planar cell polarity. Finally, the localization of Xdsh at the membrane of normal dorsal mesodermal cells is consistent with Xdsh controlling cell polarity. Our results show that polarized cell behaviour is essential for convergent extension and is controlled by vertebrate Dishevelled. Thus, a vertebrate equivalent of the Drosophila planar cell polarity signalling cascade may be required for normal gastrulation.

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Figure 1: Methods and signalling pathways.
Figure 2: Analysis of cell behaviour and polarity in Keller explants.
Figure 3: Analysis of convergent extension in Keller explants.
Figure 4: Xdsh constructs and their effects in Wnt, PCP and convergent extension assays. ++, strongly active; +, weakly active; -, weakly inhibitory; --, strongly inhibitory; nt, not tested.
Figure 5: Xdsh is localized to the membrane in cells undergoing convergent extension.

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We thank T. Grammer, M. Dionne, A. Sater, D. Keys, K. Liu and D. Frank for discussions, reading the manuscript, and blind scoring; S. Sokol for the Xdsh and Xdd1 plasmids; and D. Turner for the memEGFP plasmid. This work was supported by the NIH, NIMH and the Beckman Institute. J.B.W. was supported by NIH/NIGMS and ACS postdoctoral fellowships; B.A.R. by a US Department of Defense Breast Cancer Research Program Grant to C. Larabell; and K.M.V. by the Nathan and Violet David Scholars program at UC Berkeley.

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Correspondence to Richard M. Harland.

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Wallingford, J., Rowning, B., Vogeli, K. et al. Dishevelled controls cell polarity during Xenopus gastrulation . Nature 405, 81–85 (2000).

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