Role of Npm1 in proliferation, apoptosis and differentiation of neural stem cells

Neural tube defects (NTDs) are among the most prevalent and serious congenital malformations. And one notable teratogen that can induce NTDs is fetal exposure to hyperthermia. In our previous study, by suppression subtractive hybridization (SSH), we identified several differentially expressed genes in hyperthermia-induced NTDs. Nucleophosmin (Npm1), a multifunctional nucleolar protein, was one of the downregulated genes. For functional analysis of Npm1, we employed small interference RNA (siRNA) mediated gene silencing method with neural stem cells (NSCs). The siRNA successfully suppressed Npm1 expression at both mRNA and protein levels. As a result, suppression of Npm1 in NSCs decreased cell proliferation rate, increased apoptosis occurrence but did not seem to affect cell differentiation. Further study revealed that there was increase of p53 and p21 protein after Npm1 suppression. Taken together, our results suggest that suppression of Npm1 in NSCs inhibits cell proliferation, induces apoptosis through p53 pathway but does not affect cell differentiation. (c) 2007 Elsevier B.V. All rights reserved.