Figure 1. Hypomorphic mutations of scospondin lead to progressive scoliosis in zebrafish.

(A-B’) MicroCT images of scospondin^stl300/+ (A-A’) and scospondin^{stl300/stl300} mutant zebrafish (B-B’) at 90 dpf, in both lateral (A, B) and dorsal (A’, B’) views showing adult-viable scoliosis.

(C, D) Bright field image of the typical straight body of a wild-type (D) and atypical axial curvatures observed in homozygous scospondin^{stl297/stl297} mutant (E) larvae at 13 dpf. Scale bar is 1 mm.

(E) Dorsal-ventral axis displacement of the notochord in 5 dpf heterozygous scospondin^stl297/+ and scospondin^{stl297/stl297} mutants (n=10 and 23 respectively). (E’) Displacement is the absolute value of the dorsal-ventral (y-axis) measured against an origin set at the intersection of the first somite boundary and the dorsal edge of the notochord and propagated along the entire axis at each somite boundary for each animal.

(F) Incidence of axial curvatures over developmental time for wild type, MZscospondin^stl297, and progeny from heterozygous scospondin^stl297/+ x scospondin^{stl297/stl297} mutant crosses from both female and male homozygotes, and progeny from heterozygous scospondin^stl297/+ incrosses (mean + SD; n=112, 105, 116, 138, and 118 embryos, respectively, pooled from three independent clutches).

(G) Schematic representation of SCO-spondin protein demonstrating the location of the scospondin alleles causing with scoliosis in zebrafish. Boxes represent conserved motifs, legend in Figure S1.

(H, J) Protein alignments (Clustal-W) of SCO-spondin protein showing the sequence surrounding the amino acid residues (yellow highlight) affected by the scospondin^stl297 (H) and the scospondin^stl300 (J) mutations.

(I) A homology model of Danio rerio SCO-spondin threaded onto the LDLrA domain derived from an LDL receptor structure (6byv). The predicted disulfide bond and labeled cysteine (Cys) residues are highlighted in (H and I).

See also Figure S1–2.