负面的宫内环境常会通过表观遗传修饰改变引发胎儿宫内生长受限（FGR），继而在成年期增加罹患精神疾病的风险，而作为表观遗传调控的新成员非编码RNA（ncRNA）在这一过程中的作用研究尚不多。利用我们在ncRNA方面的特长，深入探讨ncRNA在FGR小鼠模型精神行为异常和神经发育缺陷中的调控和作用机制。我们使用单细胞测序技术，筛选在FGR小鼠的DA神经元和5-HT神经元中差异表达的ncRNA，在胚胎干细胞神经分化中观察这些ncRNA对于DA神经元和5-HT神经元分化和功能的影响，并利用转基因技术、RIP、RNA pull down、ChIP-Seq等技术阐明其作用时间段和调控机制。在此基础上，利用CRISPR技术构建转基因小鼠，观察过表达或者敲降这些ncRNA能否挽救FGR小鼠的神经发育缺陷和精神行为异常。本研究为今后以这些ncRNA作为靶标干预和治疗FGR患儿提供理论依据和实验基础。

The negative intrauterine environment often cause fetal growth restriction (FGR), and then increase the risk of psychiatric disorders in adulthood. Epigenetic modifications play important roles in FGR related diseases, but the mechanism of non-coding RNA (ncRNA) in this process is unknown. Based on our research specialty in ncRNA mechanism, we deeply explore the function and mechanism of ncRNA in the mental and behavior disorder and neural development defects of FGR mouse. In this project, we will screen the differential expressed ncRNAs in the FGR mouse DA neurons and 5-HT neurons using single-cell sequencing technique, examine the function of these ncRNAs in the embryonic stem cell neural differentiation, and explore the regulatory mechanism of these ncRNAs by RIP,RNA pull down, ChIP-Seq. Then we will construct transgenic mice by CRISPR technology, and observe whether the changes of these ncRNAs' expression level can relieve mouse nerve growth defect and mental abnormal behavior in FGR mouse. Our results will provide not only the more cues to understand the epigenetic regulatory network underlying the fetal origins neural diseases but also the theoretical basis for the therapies for the children with FGR.