SCO-spondin, a glycoprotein of the subcommissural organ/Reissner's fiber complex: evidence of a potent activity on neuronal development in primary cell cultures.

In the cattle, SCO-spondin was shown to be a brain-secreted glycoprotein specifically expressed in the subcommissural organ (SCO), an ependymal differentiation located in the roof of the Sylvian aqueduct. Furthermore, SCO-spondin makes part of Reissner's fiber (RF), a structure present in the central canal of the spinal cord. Sequencing of overlaping cDNA inserts after successive screening of a cattle SCO cDNA expression library allowed characterization of the complete sequence of this novel protein. Conserved domains were identified including twenty-six thrombospondin type 1 repeats (TSRs), nine low-density lipoprotein receptor LDLr type A domains (LDLRA), two epidermal growth factor EGF-like domains, and homologies to mucins and the von Willebrand factor were found in the amino- and carboxy- termini. In addition, SCO-spondin shows a unique arrangement "in mosaic" of these domains. The putative function of SCO-spondin in neuronal differentiation is discussed regarding these features and homologies with other developmental molecules of the central nervous system exhibiting TSR domains, and involved in axonal guidance.To correlate molecular and functional features of SCO-spondin, we tested the effect of oligopeptides whose sequences include highly conserved regions of the TSRs, LDLRA repeats, and a potent site of attachment to glycosaminoglycan, on cortical and spinal cord neurons in primary cell cultures. Peptides corresponding to SCO-spondin TSRs markedly increased adhesivity and neuritic outgrowth of cortical neurons and induced disaggregation of spinal cord neurons. Thus, SCO-spondin is a candidate to interfere with neuronal development and/or axonal guidance during ontogenesis of the central nervous system in modulating side-to-side and side-to-substratum interactions, and in promoting neuritic outgrowth. RF proper has a wide range of activity on neuronal differentiation, including survival, aggregation, and disaggregation effects and neurite extension of cortical and spinal cord neurones "in vitro." Thus, the SCO/RF complex may interact with developmental processes of the central nervous system including the posterior commissure and spinal cord differentiation.