Department of Cell Biology, Duke University, Durham, United States.
Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, United States.
Elife. 2020 Jan 29;9:e51221. doi: 10.7554/eLife.51221.
The vertebral column or spine assembles around the notochord rod which contains a core made of large vacuolated cells. Each vacuolated cell possesses a single fluid-filled vacuole, and loss or fragmentation of these vacuoles in zebrafish leads to spine kinking. Here, we identified a mutation in the kinase gene that causes fragmentation of notochord vacuoles and a severe congenital scoliosis-like phenotype in zebrafish. Live imaging revealed that Dstyk regulates fusion of membranes with the vacuole. We find that localized disruption of notochord vacuoles causes vertebral malformation and curving of the spine axis at those sites. Accordingly, in mutants the spine curves increasingly over time as vertebral bone formation compresses the notochord asymmetrically, causing vertebral malformations and kinking of the axis. Together, our data show that notochord vacuoles function as a hydrostatic scaffold that guides symmetrical growth of vertebrae and spine formation.
脊柱围绕着脊索杆组装，脊索杆包含一个由大泡状细胞组成的核心。每个泡状细胞都有一个充满液体的单一泡，斑马鱼中这些泡的丢失或碎裂会导致脊柱弯曲。在这里，我们在激酶基因中发现了一个突变，该突变导致脊索泡的碎裂，并导致斑马鱼出现严重的先天性脊柱侧凸样表型。活体成像显示 Dstyk 调节与泡融合的膜融合。我们发现，局部破坏脊索泡会导致脊柱畸形，并在这些部位弯曲脊柱轴。因此，在突变体中，随着时间的推移，随着骨形成不对称地压缩脊索，脊柱会不断弯曲，导致椎体畸形和轴弯曲。总之，我们的数据表明，脊索泡作为一个静水力学支架，指导椎体的对称生长和脊柱形成。
