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During vertebrate neurulation, extensive cell movements transform the flat neural plate into the neural tube. This dynamic morphogenesis requires the tissue to bear a certain amount of plasticity to accommodate shape and position changes of individual cells as well as intercellular cohesiveness to maintain tissue integrity and architecture. For most of the neural plate-neural tube transition, cells are polarized along the apicobasal axis. The establishment and maintenance of this polarity requires many polarity proteins that mediate cell-cell adhesion either directly or indirectly. Intercellular adhesion reduces tissue plasticity and enhances tissue integrity. However, it remains unclear how apicobasal polarity is regulated to meet the opposing needs for tissue plasticity and tissue integrity during neurulation. Here, we show that N-Cad/ZO-1 complex-initiated apicobasal polarity is stabilized by the late-onsetting Lin7c/Nok complex after the extensive morphogenetic cell movements in neurulation. Loss of either N-Cad or Lin7c disrupts neural tube formation. Furthermore, precocious overexpression of Lin7c induces multiaxial mirror symmetry in zebrafish neurulation. Our data suggest that stepwise maturation of apicobasal polarity plays an essential role in vertebrate neurulation.
Figure 10.
Apical expression of Lin7 lags behind that of ZO-1 in Xenopus laevis ( A–C ) and chicken ( D–G ) neurulation. Actin staining (green) reveals cellular and tissue morphologies. A , During medial intercalation of the neuroepithelial cells at stage 20, Lin7 (red) expression is not detectable in the frog neural fold. ZO-1 (blue; arrows) localizes to the apical side of the neural epithelial cells. B , At stage 30, Lin7 (red, arrows) localizes to the apical surface of the neural tube in frogs. C , Enlarged images of the dorsal region of the neural tube shown in B reveals that Lin7 expression lags behind that of ZO-1 in the roof plate (double arrows). Apical Lin7 expression (arrows) at the lateral walls of the neural tube is strong. Arrowheads indicate Lin7 expression at the basolateral membrane regions in the skin cells. Double arrowheads indicate the apical localization of ZO-1 at tight junctions in the skinepithelium. D , E , At the neural fold stage in chickens, weak Lin7 signal (red) is present at the basolateral membrane regions of the neuroepithelial cells. E shows a magnified local region of the epithelial wall in D . The apical surface is to the left. F , G , At the neural tube stage, a strong Lin7 signal is present at the entire apical surface of the chicken neural tube, apical to the ZO-1 staining. G shows an enlarged local region of the epithelial wall in F . Scale bars, 30 μm.
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