N-myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family, has multiple functions in cell proliferation, differentiation, and stress responses, and is predominantly expressed by astrocytes in the central nervous system. Previous studies including ours demonstrated that NDRG2 is involved in various central nervous system pathologies. However, the significance of NDRG2 in neurodevelopment is not fully understood. Here, we investigated the expression profile of NDRG2 during postnatal brain development, the role of NDRG2 in social behavior, and transcriptome changes in the brain of NDRG2-deficient mice. NDRG2 expression in the brain increased over time from postnatal day 1 to adulthood. Deletion of NDRG2 resulted in abnormal social behavior, as indicated by reduced exploratory activity toward a novel mouse in a three-chamber social interaction test. Microarray analysis identified genes differentially expressed in the NDRG2-deficient brain, and upregulated gene expression of Bmp4 and Per2 was confirmed by quantitative PCR analysis. Expression of both these genes and the encoded proteins increased over time during postnatal brain development, similar to NDRG2. Gene expression of Bmp4 and Per2 was upregulated in cultured astrocytes isolated from NDRG2-deficient mice. These results suggest that NDRG2 contributes to brain development required for proper social behavior by modulating gene expression in astrocytes.

N-myc下游调节基因2（NDRG2）是NDRG家族的成员，在细胞增殖，分化和应激反应中具有多种功能，并且主要由中枢神经系统中的星形胶质细胞表达。包括我们在内的先前研究表明，NDRG2参与了各种中枢神经系统病理。但是，NDRG2在神经发育中的意义尚未完全了解。在这里，我们调查了出生后大脑发育过程中NDRG2的表达概况，NDRG2在社交行为中的作用以及NDRG2缺陷小鼠大脑中转录组的变化。从出生后第1天到成年，NDRG2在大脑中的表达随时间增加。删除NDRG2会导致异常的社交行为，如三室社交互动测试中对新型小鼠的探索活动减少所表明的。微阵列分析鉴定了在NDRG2缺陷型大脑中差异表达的基因，并上调了该基因的表达通过定量PCR分析确认了Bmp4和Per2。这些基因和编码蛋白的表达在出生后大脑发育过程中均随时间增加，与NDRG2相似。Bmp4和Per2的基因表达在从NDRG2缺陷小鼠分离的星形胶质细胞中表达上调。这些结果表明，NDRG2通过调节星形胶质细胞中的基因表达，促进了正常社交行为所需的大脑发育。