Exmental Studies on the mechanisum of neural tube defect

神经管缺陷机制的实验研究

• 批准号: 07671540
• 负责人: ARAI Hajime
• 金额: $ 0.96万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671540/
• 关键词: Helix-loop-helix transcription factor; chick embryo; neural tube; neurogenesis; molecular biology; Helix-loop-helix (HLH) transcription factor:; Helix-loop-helix transcription factors

3Helix-loop-helix (HLH) transcription factors play a critical role in neural tube development. Three class A basic HLH transcription factors are present in the developing chick neural tube whereas GE1, GE12 is expressed in interneurons and not in motoneurons. Simultaneous blocking of known class A bHLH transcription factors which are expressed in the neural tube by antisense oligonucleotides results in death of differentiating interneurons and has no detectable effect on cell cycle or DNA synthesis in vitro. Blocking the expression of individual class A bHLH transcription factors results no detectable effect. These results demonstrate that GEs are involved in the differentiation of interneurons and have a functional redundancy during neuronal development. Following this study, we established neural plate explant culture from early chick embryo and examine whether neural tube defect occurs or not by blocking their expressions of GEs using antisense oligonucletoides. We added antisense oligonucleotides into single cells by microinjectin. However, neural tube defect did not occur. These experiments suggest that a single gene mutation does not cause neural tube defects.

3螺旋-环-螺旋（Helix-loop-helix，HLH）转录因子在神经管发育过程中起重要作用。三个A类基本HLH转录因子存在于发育中的鸡神经管中，而GE 1，GE 12在中间神经元中表达，而不在运动神经元中表达。通过反义寡核苷酸同时阻断已知的在神经管中表达的A类bHLH转录因子导致分化中的中间神经元死亡，并且在体外对细胞周期或DNA合成没有可检测的影响。阻断单个A类bHLH转录因子的表达不会产生可检测的影响。这些结果表明，GEs参与了中间神经元的分化，并在神经元发育过程中具有功能冗余。本研究建立了早期鸡胚神经板组织块培养体系，并利用反义寡核苷酸阻断其表达，检测神经管畸形的发生与否。我们通过显微注射将反义寡核苷酸加入到单个细胞中。但未发生神经管畸形。这些实验表明，单个基因突变不会导致神经管缺陷。