Laboratory of Sensory Cell Biology & Organogenesis, Centre de Regulació Genòmica-CRG, c/Dr Aiguader 88, Barcelona 08003, Spain.
Development. 2011 Mar;138(6):1143-52. doi: 10.1242/dev.060566.
Bilateral symmetric tissues must interpret axial references to maintain their global architecture during growth or repair. The regeneration of hair cells in the zebrafish lateral line, for example, forms a vertical midline that bisects the neuromast epithelium into perfect mirror-symmetric plane-polarized halves. Each half contains hair cells of identical planar orientation but opposite to that of the confronting half. The establishment of bilateral symmetry in this organ is poorly understood. Here, we show that hair-cell regeneration is strongly directional along an axis perpendicular to that of epithelial planar polarity. We demonstrate compartmentalized Notch signaling in neuromasts, and show that directional regeneration depends on the development of hair-cell progenitors in polar compartments that have low Notch activity. High-resolution live cell tracking reveals a novel process of planar cell inversions whereby sibling hair cells invert positions immediately after progenitor cytokinesis, demonstrating that oriented progenitor divisions are dispensable for bilateral symmetry. Notwithstanding the invariably directional regeneration, the planar polarization of the epithelium eventually propagates symmetrically because mature hair cells move away from the midline towards the periphery of the neuromast. We conclude that a strongly anisotropic regeneration process that relies on the dynamic stabilization of progenitor identity in permissive polar compartments sustains bilateral symmetry in the lateral line.
双侧对称组织必须解释轴向参考，以在生长或修复过程中保持其整体结构。例如，斑马鱼侧线毛细胞的再生形成了一条垂直的中线，将神经丘上皮分为完美的镜像对称的平面极化两半。每一半都包含相同平面取向的毛细胞，但与对面一半的取向相反。这个器官的双侧对称性的建立还知之甚少。在这里，我们表明毛细胞的再生是沿着垂直于上皮平面极性的轴强烈定向的。我们证明了神经丘中的 Notch 信号的分区，并表明定向再生取决于具有低 Notch 活性的极性区中毛细胞前体细胞的发育。高分辨率活细胞跟踪揭示了一种新的平面细胞反转过程，即姊妹毛细胞在亲代细胞分裂后立即反转位置，表明定向的前体细胞分裂对于双侧对称性是可有可无的。尽管再生总是有方向性的，但上皮的平面极化最终会以对称的方式传播，因为成熟的毛细胞会从中线向神经丘的外围移动。我们得出的结论是，一种强烈各向异性的再生过程，依赖于在许可的极性区中维持祖细胞身份的动态稳定，维持了侧线的双侧对称性。
