TCTP is Essential for Cell Proliferation and Survival during CNS Development

Abstract

Translationally controlled tumor-associated protein (TCTP) has been implicated in cell growth, proliferation, and apoptosis through interacting proteins. Although TCTP is expressed abundantly in the mouse brain, little is known regarding its role in the neurogenesis of the nervous system. We used Nestin-cre-driven gene-mutated mice to investigate the function of TCTP in the nervous system. The mice carrying disrupted TCTP in neuronal and glial progenitor cells died at the perinatal stage. The NestinCre/+; TCTPf/f pups displayed reduced body size at postnatal day 0.5 (P0.5) and a lack of milk in the stomach compared with littermate controls. In addition to decreased cell proliferation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase assay revealed that apoptosis was increased in newly committed TCTP-disrupted cells as they migrated away from the ventricular zone. The mechanism may be that the phenotype from specific deletion of TCTP in neural progenitor cells is correlated with the decreased expression of cyclins D2, E2, Mcl-1, Bcl-xL, hax-1, and Octamer-binding transcription factor 4 (Oct4) in conditional knockout mice. Our results demonstrate that TCTP is a critical protein for cell survival during early neuronal and glial differentiation. Thus, enhanced neuronal loss and functional defect in Tuj1 and doublecortin-positive neurons mediated through increased apoptosis and decreased proliferation during central nervous system (CNS) development may contribute to the perinatal death of TCTP mutant mice.