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.
Highlights
Controlled tumor-associated protein (TCTP) is a highly conserved and abundantly expressed protein that has been implicated in both cell growth and the human acute allergic response.TCTP is widely expressed in many tissues and cell types [1], and its protein levels are highly regulated in response to a wide range of extracellular signals and cellular conditions [2]
We demonstrated that TCTP plays a critical role in survival at the mid-embryonic stage, but its role and functional mechanism in the regulation of neurogenesis at the early stage of brain development remains unknown
We found that TCTP expression in the ventricular zone was dramatically decreased to a low level from E16.5 to P0.5 but increased in the cortical layer
Summary
Controlled tumor-associated protein (TCTP) is a highly conserved and abundantly expressed protein that has been implicated in both cell growth and the human acute allergic response. TCTP is widely expressed in many tissues and cell types [1], and its protein levels are highly regulated in response to a wide range of extracellular signals and cellular conditions [2]. TCTP has been shown to interact with tubulin [3], Na+ , K+ -ATPase [4], mammalian Plk [5], translation elongation factors eEF1A and eEF1Bbeta [6,7], TSAP6 [8], Mcl-1 [9], Bcl-XL [10], vitamin D3 receptor (VDR) [11], and p53 [12] for cell cycle regulation, protein synthesis, and antiapoptosis. We demonstrated that TCTP functions as an antiapoptotic protein required for mouse embryonic development and survival in
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