Cug2 is essential for normal mitotic control and CNS development in zebrafish

To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate.Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders.Cancer-upregulated gene 2 (CUG2) is known to be differentially expressed in multiple human cancer tissues including the ovary, liver, lung, intestines and pancreas [1]. Mammalian cells overexpressing CUG2 showed hallmarks of neoplasmic transformation in vitro, such as increased cell proliferation, migration, invasion, anchorage-independent growth and tumor formation in nude mice, similar to the effects of the H-ras oncogene [1].Recently, CUG2 was shown to interact with CENP-T and CENP-A, essential components of the nucleosome complex located at the centromere, and was hence named centromere protein W (CENP-W) [2,3]. The centromere is involved in sister chromatid cohesion and the attachment of spindle microtubules, and is thus responsible for accurate chromosome segregation during mitotic and meiotic cell division [4]. CENP-A, a histone H3-like core protein, is required for the recruitment of many constitutive centromere components as well as transient kinetochore components [5,6]. We and others have reported that CUG2/CENP-W forms a DNA-binding complex together with the CENP-T and CENP-A as part of the centromere chromatin structure [2,3]. SiRNA-mediated knockdown of CUG2/CENP-W in HeLa cells caused defective mitosis characterized by multipolar spindle forma