RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Cell. 2012 May 25;149(5):1084-97. doi: 10.1016/j.cell.2012.04.021.
Neural-tube closure is a critical step of embryogenesis, and its failure causes serious birth defects. Coordination of two morphogenetic processes--convergent extension and neural-plate apical constriction--ensures the complete closure of the neural tube. We now provide evidence that planar cell polarity (PCP) signaling directly links these two processes. In the bending neural plates, we find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens junctions (AJs) oriented toward the mediolateral axes of the plates. At these AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized manner. This planar-polarized contraction promotes simultaneous apical constriction and midline convergence of neuroepithelial cells. Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate.
神经管闭合是胚胎发生的一个关键步骤，其失败会导致严重的出生缺陷。两种形态发生过程——会聚延伸和神经板顶壁收缩的协调，确保了神经管的完全闭合。我们现在提供的证据表明，平面细胞极性（PCP）信号直接将这两个过程联系起来。在弯曲的神经板中，我们发现一个调节 PCP 的钙黏蛋白 Celsr1 集中在沿着板的中侧轴排列的黏着连接（AJs）中。在这些 AJs 处，Celsr1 与 Dishevelled、DAAM1 和 PDZ-RhoGEF 合作，上调 Rho 激酶，导致它们以平面极化的方式依赖肌动球蛋白收缩。这种平面极化的收缩促进神经上皮细胞的顶端收缩和中线汇聚。我们的研究结果表明，PCP 信号赋予 AJs 各向异性的收缩性，产生细胞力，促进神经板的极化弯曲。
