神经管发育缺陷（NTDs）是最严重、最常见的出生缺陷疾病之一。神经干细胞（NSCs）的增殖、分化、迁移等过程是神经管发育的细胞学基础，SoxB1家族是调控NSCs增殖分化的重要转录因子，NTDs患者表现出SoxB1缺失或表达显著降低的现象。本课题前期研究发现抑制斑马鱼SoxB1家族成员Sox19b，胚胎表现出前脑减小甚至缺失，尾部向上弯曲等NTDs表型，并首次发现神经管中NSCs过早分化，重要表观遗传因子Ezh2的表达显著降低。本研究拟在前期研究基础上，通过组织切片、原位杂交、qPCR等技术，探讨Sox19b在NTDs中的作用和对NSCs的调控机制；利用透射电镜、ChIP等技术，研究染色质结构、组蛋白修饰的变化，阐明调控Ezh2的分子机制。本研究揭示了Sox19b在NTDs中的新作用，建立了转录因子与表观遗传因子对NSCs的调控网络，为NTDs的临床治疗提供新的线索和理论指导。

Neural Tube Defects (NTDs) is the most serious and common disease of the birth defects. The proliferation, differentiation and migration of the neural stem cells (NSCs) is the cellular basis of neural tube development. The transcription factor SoxB1 has a curial role in controlling the proliferation and differentiation of the NSCs. A significant decreased or totally lost of SoxB1 expression was found in NTDs’ patients. Our preliminary data demonstrated that the inhibition of Sox19b induced many NTDs phenotypes (e.g. narrowed forebrain and curved tail), premature differentiation of NSCs in neurons, and remarkable reduced expression of epigenetic factors Ezh2. On the basis of above finding, we will determine the role Sox19b in NTDS and the mechanism(s) through which Sox19b contributes to NSCs by utilizing histologic section, in situ hybridization, qPCR, etc. We next use TEM and ChIP to dissect the role of Ezh2 in chromatin remodeling, histone modification in mediating NTDs outcomes. This study will determine the roles of Sox19 in NTDs and establish a network of gene regulation in NSCs in genetic and epigenetic levels, thereby shed light on the future strategies for therapeutic targeting.