**1. Introduction**

Translationally 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<sup>+</sup>, K<sup>+</sup>-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.

TCTP is also known as a histamine-releasing factor that stimulates the secretion of histamine [13]. In addition, decreased TCTP levels have been detected in certain areas of postmortem brains from Down syndrome and Alzheimer's patients [14]. In previous studies, we demonstrated that TCTP functions as an antiapoptotic protein required for mouse embryonic development and survival in systemic knockout mice [15]. Endoderm markers', such as Shh and PECAM, expression patterns

were markedly reduced in embryonic day 9.5 (E9.5) TCTP−/− embryos, especially in the forebrain and midbrain anterior end. Furthermore, TCTP plays a very modest role in thymocyte development but is critical for peripheral T cell maintenance and TCR-mediated cell proliferation [16]. TCTP is also essential for developmental β-cell mass establishment and adaptation in response to insulin resistance [17]. Recent studies demonstrated that the interacting proteins of TCTP, such as Mcl-1 and Bcl-xL, play roles in the brain. Mcl-1 is a key regulator of apoptosis during the development of the central nervous system (CNS) [18]. Bcl-xL germline-deficient mice also undergo embryonic death at E13 and show increased apoptotic activity in the brain [19]. The conditional disruption of Bcl-xL in catecholaminergic neurons results in viable mice, with the catecholaminergic neuronal population reduced by one-third [20]. These studies sugges<sup>t</sup> that TCTP may play an important role in CNS development. However, despite the importance of TCTP in the regulation of apoptosis, the impact of TCTP disruption during CNS development has not been investigated, except one recent paper that showed that TCTP may be implicated in the regulation of visual axon development of *Xenopus laevis* [21]. Therefore, the neuronal function of TCTP in the brain requires further investigation.

In the present work, we generated and characterized the phenotype of *TCTP* mutant mice and determined the possible mechanisms involved. We showed with a mouse model that TCTP is required for neural development in mammals. Deficiency of TCTP in neuronal and glial cell precursors resulted in decreased bromodeoxyuridine (BrdU) incorporation, increased widespread apoptosis, and disturbance of Tuj1-positive cell maturation, subsequently leading to perinatal death of TCTP mutant mice. Taken together, our results demonstrate that TCTP is required for the survival and di fferentiation of neuronal progenitor cells and is essential for cortical neurogenesis in development.
