The Reissner Fiber in the Cerebrospinal Fluid Controls Morphogenesis of the Body Axis
The Reissner Fiber in the Cerebrospinal Fluid Controls Morphogenesis of the Body Axis
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DOI：
10.1016/j.cub.2018.05.079
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发表时间：
2018-08-06
期刊：
影响因子：
9.2
通讯作者：
Bardet, Pierre-Luc
中科院分区：
文献类型：
--
作者：
Cantaut-Belarif, Yasmine;Sternberg, Jenna R.;Bardet, Pierre-Luc
器官的发育依赖于细胞间协调的远程通讯的整合。脑脊液成分和流动特性调节中枢神经系统发育的几个方面，包括祖细胞增殖、神经发生和迁移[1-3]。一个未充分研究的脑脊液成分，描述了超过世纪前的脊椎动物，是Reissner纤维。在发育早期形成的这种细胞外线是由SCO-spondin蛋白在第三和第四脑室和脊髓中央管中的组装引起的[4]。到目前为止，Reissner纤维的功能仍然难以捉摸，部分原因是缺乏遗传失效模型[4]。在这里，通过突变的scospondin基因，我们表明，Reissner纤维是一个直的后体轴的形态发生的关键。在Reissner纤维丢失的斑马鱼突变体中，纤毛发生和脑脊液流动是完整的，但体轴形态发生受损。我们的研究结果也解释了经常观察到的表型，突变体胚胎与缺陷纤毛表现出缺陷的体轴曲率。在这里，我们揭示了这些突变体系统地组装Reissner纤维失败。我们表明，纤毛促进Reissner纤维的形成和纤维是必要的适当的身体轴形态发生。我们的研究为将来研究脊椎动物发育过程中Reissner纤维与体轴曲率控制的机制奠定了基础。
Organ development depends on the integration of coordinated long-range communication between cells. The cerebrospinal fluid composition and flow properties regulate several aspects of central nervous system development, including progenitor proliferation, neurogenesis, and migration [1-3]. One understudied component of the cerebrospinal fluid, described over a century ago in vertebrates, is the Reissner fiber. This extracellular thread forming early in development results from the assembly of the SCO-spondin protein in the third and fourth brain ventricles and central canal of the spinal cord [4]. Up to now, the function of the Reissner fiber has remained elusive, partly due to the lack of genetic invalidation models [4]. Here, by mutating the scospondin gene, we demonstrate that the Reissner fiber is critical for the morphogenesis of a straight posterior body axis. In zebrafish mutants where the Reissner fiber is lost, ciliogenesis and cerebrospinal fluid flow are intact but body axis morphogenesis is impaired. Our results also explain the frequently observed phenotype that mutant embryos with defective cilia exhibit defects in body axis curvature. Here, we reveal that these mutants systematically fail to assemble the Reissner fiber. We show that cilia promote the formation of the Reissner fiber and that the fiber is necessary for proper body axis morphogenesis. Our study sets the stage for future investigations of the mechanisms linking the Reissner fiber to the control of body axis curvature during vertebrate development.