The Reissner Fiber in the Cerebrospinal Fluid Controls Morphogenesis of the Body Axis

Yasmine Cantaut-Belarif,Jenna R Sternberg,Olivier Thouvenin,Claire Wyart,Pierre-Luc Bardet

doi:10.1016/j.cub.2018.05.079

Abstract

SummaryOrgan 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, 2, 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.

Highlights

In all mutant embryos for both scospondin alleles, we observed as early as 24 hpf (i.e., 6 hr prior to the emergence of the curled-down phenotype) the lack of the Reissner fiber in the third brain ventricle and in the central canal (Figure 1D)
By mutating the scospondin gene, we demonstrate that the Reissner fiber is critical for the morphogenesis of a straight posterior body axis
We show that cilia promote the formation of the Reissner fiber and that the fiber is necessary for proper body axis morphogenesis

Summary

Introduction

In all mutant embryos for both scospondin alleles, we observed as early as 24 hpf (i.e., 6 hr prior to the emergence of the curled-down phenotype) the lack of the Reissner fiber in the third brain ventricle and in the central canal (Figure 1D). Because the signal peptide is unaffected by the insertion, this observation suggests that the abnormal protein is still secreted into the CSF but fails to form a fiber. These data demonstrate that compromising the assembly of SCO-spondin into the Reissner fiber in the CSF disrupts the curvature of the posterior axis during embryogenesi

Methods

Results

Conclusion