细胞迁移在早期胚胎发育等生物学过程中发挥重要作用，但其分子调控机制尚不清楚。本课题组一直致力于细胞核分布基因C（Nuclear distribution gene C，NudC）家族的功能研究。近期结果显示，细胞核分布基因NudCL2（NudC-like gene 2）敲除将导致小鼠胚胎致死且伴随脑部发育缺陷等细胞迁移异常相关表型；在细胞水平敲除NudCL2则可抑制细胞迁移；定量质谱分析NudCL2敲除后下调的分子，发现细胞迁移调控相关基因TSC2（Tuberous Sclerosis Complex 2）敲除胚胎表型与NudCL2敲除最相似，并可与NudCL2互作。上述结果提示，NudCL2可能通过调节TSC2蛋白稳定性来参与细胞迁移调控，进而影响小鼠胚胎发育。本项目拟在分子、细胞及动物水平研究NudCL2在细胞迁移及小鼠胚胎发育过程中的作用及机制，为细胞迁移异常相关疾病的诊治提供线索。

It is reported that cell migration contributes to amount of biological processes, including various events of early embryonic development. However, the underlying molecular mechanism that controls cell migration remains unclear. We focus on the biological function of nuclear distribution gene C (Nuclear distribution gene C, NudC) family for many years. We established NudCL2 (NudC-like gene 2) gene knockout mice and found that homozygous state is lethal in mid-gestation with severe embryonic malformations related to the defects of migration such as neural tube defects. Furthermore, Our data showed that knockout of NudCL2 significantly inhibits cell migration process in cells. Moreover, quantitative mass spectrometry was applied to identify differentially expressed proteins in NudCL2 knockout and wildtype mouse embryo. The data indicated that knockout of NudCL2 results in the decrease of TSC2 (Tuberous Sclerosis Complex 2) protein level. The similar role of TSC2 in cell migration and embryonic development is reported and prompted us to investigate the biochemical relationship between it and NudCL2. Our immunoprecipitation data revealed that NudCL2 can interact with TSC2 protein in vivo. Thus, we propose that NudCL2 may play important role in cell migration during mouse embryonic development by stabilizing TSC2. In this proposal, we will systematically characterize the biological function of NudCL2 in cell migration and mouse embryonic development, and elucidate its possible molecular mechanism at molecular, cellular and animal levels. This study will provide novel potential therapeutic targets for the human diseases related to the dysfunction of cell migration.