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Although Rho-GTPases are well-known regulators of cytoskeletal reorganization, their in vivo distribution and physiological functions have remained elusive. In this study, we found marked apical accumulation of Rho in developing chick embryos undergoing folding of the neural plate during neural tube formation, with similar accumulation of activated myosin II. The timing of accumulation and biochemical activation of both Rho and myosin II was coincident with the dynamics of neural tube formation. Inhibition of Rho disrupted its apical accumulation and led to defects in neural tube formation, with abnormal morphology of the neural plate. Continuous activation of Rho also altered neural tube formation. These results indicate that correct spatiotemporal regulation of Rho is essential for neural tube morphogenesis. Furthermore, we found that a key morphogenetic signaling pathway, the Wnt/PCP pathway, was implicated in the apical accumulation of Rho and regulation of cell shape in the neural plate, suggesting that this signal may be the spatiotemporal regulator of Rho in neural tube formation.
Figure 7. Inhibition of Wnt/PCP pathway causes neurulation defects and disrupts the apical accumulation of Rho in neural plate cells in Xenopus embryos. (A) mRNA injection experiment in embryos. mRNA was injected into two right-side blastomeres of the animal hemisphere at the eight-cell stage. Venus mRNA (50 pg) was coinjected as a marker. At the neurula stage, injected mRNA was distributed mainly to the right side of the ectoderm. (B) Phenotypes of embryos at the neurula stage producing mutant molecules that inhibit the Wnt/PCP pathway. Top row contains bright microscopy images; middle row shows images of Venus distribution; bottom row contains sketches depicting the morphology as transverse sections. Normal, a Venus-expressing control neurulaembryo. Mild and Severe, dominant-negative dishevelled (Xdd1)-expressing embryos with mild and severe phenotypes, respectively. In mild cases, the medial line is almost straight and the neural plate of the mRNA-injected side is broader than that of uninjected control side. In severe cases, medial lines are curved toward the injected side, and the neural plates of the injected side are much broader than those of the control side. Black lines indicate sides of neural folds. Dotted lines represent medial line of embryos. (C) Transverse sections of control (a–c), Xdd1 mRNA (200 pg)-injected (d–f), and Xdd1 plus wild-type disheveled (Xdsh, 400 pg) mRNA-injected (g–i) embryos. Venus (a, d, and g), Rho (b, e, and h), and merged (c, f, and i) images. (j) Statistics of the phenotypes induced by Xdd1 injection and coinjection with Xdsh. Venus: n = 138; Venus + Xdd1: n = 130; Venus + Xdd1 + Xdsh: n = 102. (D) Transverse sections of XFrz7-dC mRNA (400 pg)-injected (a–c) and XWnt11-dC mRNA (400 pg)-injected (d–f) embryos. Venus (a and d), Rho (b and e), and merged (c and f) images. (g) Statistics of the phenotypes induced by Xfrz7-dC- or Xwnt11-dC-injection. Venus: n = 138; Venus + XFrz7-dC: n = 93; Venus + XWnt11-dC: n = 90. Broken lines in C and D represent outlines of neural plates. Dotted lines represent medial lines of embryos. (C and D) Arrowheads, the region of apical accumulation of Rho; open arrowheads, disruption of apical accumulation of Rho. Scale bars, 50 μm. (E) Dorsal views of neural plate cells in control and Xdd1 mRNA-injected embryos. (a and b) Arrangements of neural plate cells of (a) Venus- and (b) Venus + Xdd1 mRNA-injected Xenopus embryos. (c and d) Dorsal scanning electron microscopic views of the neural grooves of Venus- (c) and Venus + Xdd1 (d) mRNA-injected Xenopus embryos. Scale bar, 10 μm. (e) Statistics of apical surface area of neural plate cell. In the Xdd1-injected side, the apical surface area of neural plate cells is much larger than in the uninjected control side, whereas in Venus-injected embryos, neural plate cells on both sides have almost the same apical surface area. Venus: n = 20, 4 specimens; Xdd1: n = 20, 3 specimens. Bars, mean + SEM.
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