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Ependymal cells form a mostly single-layered epithelium at the surfaces of the cerebral ventricles. In order to gain insight into their function, a subtractive cDNA library of ependyma minus brain was screened for novel ependymaspecific proteins. One of the identified candidates is a WD40 repeat protein provisionally designated SCO-C3. It is abundantly expressed in testis and cultured ependymal cells. Low levels are found in lung and brain, respectively, while it is absent from kinocilia-free tissues. In testis and ependymal primary cultures, SCO-C3 mRNA appears concomitantly with the messages for sperm-associated antigen 6, a kinocilia marker, and for hydin, a protein linked to ciliary function and hydrocephalus. In testis, ependyma and respiratory epithelium, the SCO-C3 protein is upregulated together with kinocilia formation. The sco-c3 gene is restricted to genera in possession of kinocilia, and it is strongly conserved during evolution. The human and zebrafish proteins are identical in 62% of their aligned amino acids. On the mRNA level, the zebrafish SCO-C3 ortholog was found only in kinocilia-bearing tissues by in situ hybridisation. Gene knockdown in zebrafish embryos by antisense MO injection resulted in severe hydrocephalus formation with unaltered ependymal morphology or ciliary beat. SCO-C3 can be considered a differentiation marker of kinocilia-bearing cells, where it may function in generation or maintenance of cell polarity. from Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft für Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system Witten, Germany. 28–30 September 2006

SCO-C3 upregulation is tied to kinocilia formation, and gene knockdown causes hydrocephalus in zebrafish