Subcommissural organ/Reissner's fiber complex: Characterization of SCO-spondin, a glycoprotein with potent activity on neurite outgrowth

In the developing vertebrate nervous system, several proteins of the thromb ospondin superfamily act on axonal pathfinding. By successive screening of a SCO-cDNA library, we have characterized a new member of this superfamily, which we call SCO-spondin. This extracellular matrix glycoprotein of 4,560 amino acids is expressed and secreted early in development by the subcommi ssural organ (SCO), an ependymal differentiation located in the roof of the Sylvian aqueduct. Furthermore, SCO-spondin makes part of Reissner's fiber (RF), a thread-like structure present in the central canal of the spinal co rd. This novel protein shows a unique arrangement of several conserved doma ins, including 26 thrombospondin type 1 repeats (TSR), nine low-density lip oprotein receptor (LDLr) type A domains, two epidermal growth factor (EGF)- like domains, and N- and C-terminal von Willebrand factor (vWF) cysteine-ri ch domains, all of which are potent sites of protein-protein interaction. R egarding the huge number of TSR, the putative function of SCO-spondin on ax onal guidance is discussed in comparison with other developmental molecules of the CNS exhibiting TSR. To correlate SCO-spondin molecular feature and function, we tested the effect of oligopeptides, whose sequences include hi ghly conserved amino acids of the consensus domains on a neuroblastoma cell line B 104. One of these peptides (WSGWSSCSRSCG) markedly increased neurit e outgrowth of B 104 cells and this effect was dose dependent. Thus, SCO-sp ondin is a favorable substrate for neurite outgrowth and may participate in the posterior commissure formation and spinal cord differentiation during ontogenesis of the central nervous system. (C) 2000 Wiley-Liss, Inc.