申请人首次报道了miR-200b能通过CITED2促进细胞凋亡导致神经管畸形（NTDs）的产生。本课题预实验中，我们利用RNA-seq首次发现了一个转录因子NFI-C在NTDs小鼠中表达升高，而且预测显示NFI-C是miR-200家族的转录调节因子。进一步我们发现并证明了miR-200家族的两个新的靶基因，自噬相关基因Ambra1和Atg5。因此我们推测，NFI-C通过调节miR-200家族转录，抑制Ambra1和Atg5表达，减少细胞自噬，进而破坏细胞增殖、分化与凋亡平衡，最终导致NTDs。本研究中我们拟以NFI-C/miR-200家族/Ambra1、Atg5为主轴，用维甲酸灌胃制作的NTDs动物模型以及采用NFI-C转基因鼠和敲除鼠，研究此通路中各个因子间的调节关系，明确它们对细胞自噬、增殖、分化与凋亡的影响，为揭示NTDs发生发展机制和寻找新的临床治疗干预靶点提供重要的研究基础。

We first reported that miR-200b can induce apoptosis leading to NTDs (Neural tube defects) through its target gene CITED2. Our preliminary studies found that a transcription factor, NFI-C, significantly increased in NTDs by using RNA-seq and it is predicted as a putative transcriptional regulator for miR-200b family. We also identified two novel target genes of miR-200 family, autophagy related gene Ambra1 and Atg5. Based on our findings, we hypothesize that NFI-C-suppressed Ambra1 and Atg5 through regulating miR-200s inhibit autophagy, impacting cell proliferation, differentiation and apoptosis, which is essential for neural tube closure. In the current study, we employ a retinoic acid-induced NTDs mouse model as well as NFI-C transgenic/knockout mouse model to investigate the relationship of NFI-C/miR-200s /Ambra1, Atg5, to demonstrate the function and mechanism of this axis in autophagy, proliferation, differentiation and apoptosis of NTDs. This project will provide scientific evidence for understanding for pathogenesis and new therapeutic treatments of NTDs.