Nusap1 is essential for neural crest cell migration in zebrafish

Abstract

Microtubules play important roles in mitotic spindle assembly and chromosome segregation to maintain normal cell cycle progression. A number of microtubule-associated proteins have been identified in epithelial and neural cell cultures; however, their physiological significance is not well characterized due to the lack of appropriate in vivo animal models. Nucleolar spindleassociated protein (NuSAP) is a microtubule-binding protein and is reported to be involved in mitosis by cell culture studies. In this report, we identified the zebrafish homologue of human NuSAP and investigated its expression profile and functions. Using in situ hybridization, we demonstrated that transcripts of zebrafish nusap1 are specifically expressed in the retina, forebrain, hindbrain and neural crest. When the in vivo expression of nusap1 was knocked down through antisense oligonucleotide morpholino technology, the morphants of nusap1 showed impaired morphogenesis in the trunk and yolk extension, implying the involvement of Nusap1 in cell migration. Mechanistic studies revealed that nusap1 morphants have an altered expression pattern of neural crest markers crestin and sox9b, but normal expression of blood vessel and notochord markers gata1 and shh. In addition, nusap1 mRNA injection caused serious apoptosis in retina and hindbrain tissue, and these phenotypes can be rescued by co-injection of morpholino against nusap1. These observations not only suggest a role for Nusap1 in connecting apoptosis with cell migration, but also provide strong evidences that Nusap1 is potentially involved in morphogenesis in vertebrates.

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma

“…A study by Gordon et al (23) demonstrated that knockdown of NUSAP1 by siRNA reduced the proliferation and invasion in prostate cancer cell lines, suggested that NUSAP1 could influence tumor cell growth and aggressiveness. Furthermore, Nie et al (24) found that NUSAP1 depletion blocked the migration of neural crest cells in zebrafish embryos, which indicates that its overexpression may promote cancer cell migration. As we mentioned earlier, NUSAP1 is a microtubule-binding protein that is selectively expressed in proliferating cells.…”

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome

“…Several genes identified in our dataset, including Cdk1 , Cenpf , Nusap1 , Aurkb , and Tacc3 play a crucial role in brain development and function, and their dysregulation is associated with neuro-developmental or neurodegenerative conditions [Camargo et al, 2007; Schick et al, 2007; Nie et al, 2010; Marchal et al, 2011; Yang et al, 2012; Satoh et al, 2013]. …”

“…Expression of these genes is tightly regulated through very complex mechanisms and their gene dosage alteration is associated with developmental defects and cancer [Rieder and Salmon, 1998;Stewart et al, 2003;Santamaria and Ortega, 2006]. Several genes identified in our dataset, including Cdk1, Cenpf, Nusap1, Aurkb, and Tacc3 play a crucial role in brain development and function, and their dysregulation is associated with neurodevelopmental or neurodegenerative conditions [Camargo et al, 2007;Schick et al, 2007;Nie et al, 2010;Marchal et al, 2011;Yang et al, 2012;Satoh et al, 2013].…”

Suppression of GSK3β by ERK mediates lipopolysaccharide induced cell migration in macrophage through β-catenin signaling

“…Immunoprecipitation was performed as previously described (Zhang et al, 2004;Nie et al, 2010;Zhang et al, 2012b;Zhou et al, 2012b); Immunoblotting was performed with specific primary antibody as indicated and secondary anti-mouse or anti-rabbit antibodies that were conjugated to horseradish peroxidase (Amersham Biosciences). Proteins were visualized by chemiluminescence.…”