What is Scospondin and the Reissner Fiber?

Scospondin is a highly conserved glycoprotein that is secreted by the subcommissural organ of the brain into the ventricular space (Sepulveda et al., 2021). Cilia-driven fluid flow facilitates the aggregation of scospondin monomers into the Reissner Fiber (RF), which treadmills down the central canal of the spinal cord in the caudal direction (Troutwine et al., 2020). The RF is highly conserved across chordates and has been observed in over 200 vertebrate species (Aboitiz & Montiel, 2021), yet the function is still largely unknown. However, recent analyses in zebrafish suggest that it may play a role in the development of a straight body axis (Cantaut-Belarif et al., 2018; Troutwine et al., 2020; Orts-Del'Immagine et al., 2020; Rose et al., 2020; Lu et al., 2020, Gray et al., 2021). In this regard, Troutwine et al. (2020) demonstrated that homozygous mutants of the stl300 C-878-S allele present with progressive loss of the RF and whole-body scoliosis. Despite its prevalence across chordates and importance in development, the structure of scospondin has not been experimentally determined. This is likely due to its large size (4990 residues; 540 kD) and tendency to form insoluble aggregates. Therefore this project aims to use computational tools, including AlphaFold2 (Jumper et al., 2021a and 2021b), to predict the structure of scospondin as well as investigate the implications of the stl300 mutation.