MOLECULAR GENETICS OF EARLY NEUROGENESIS

早期神经发生的分子遗传学

• 批准号: 6165423
• 负责人: ETHAN BIER
• 金额: $ 28.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6165423
• 关键词: Drosophilidae; Xenopus; alleles; chemical binding; developmental genetics; embryogenesis; fusion gene; gene deletion mutation; gene expression; genetic enhancer element; genetic promoter element; genetic regulation; genetic regulatory element; genetic transcription; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rabbit; laboratory rat; neurogenesis; neurogenetics; nucleic acid sequence; phenotype; point mutation; polymerase chain reaction; transcription factor

In this proposal we describe experiments to extend our previous analysis of the scratch (scrt) gene which encodes a pan-neural transcription factor likely to function as a repressor of non-neuronal gene expression (Specific Aim l). We also propose to follow a new line of investigation focused on the analysis of the short gastrulation (sog) gene, which we isolated in the course of our studies of pan-neural enhancer elements. sog is expressed in the early neuroectoderm and encodes likely antagonist of the TGFbeta-like Dpp signaling pathway (Specific Aims II-IV). Sog and the Dpp signaling pathway have been highly conserved during evolution. Dpp and its vertebrate homologue BMP-4 can functionally substitute for each other in dorsalventral pattern formation in flies and in bone morphogenesis in vertebrates. In addition, a Xenopus homologue of sog known as chordin has been identified recently. Like sog and dpp in flies, chordin and BMP-4 also have opposing effects on dorsal-ventral patternIng. Thus, it is likely that the sog,/chordin and dpp/BMP-4 genes play conserved roles in early dorsal-ventral patterning in invertebrates and vertebrates. These studies are therefore highly relevant to understanding the regulation of growth factors in the TGFbeta superfamily. Specific research goals are to: I. Determine how the pan-neural genes scratch and deadpan collaborate to promote neurogenesis. II. Determine whether sog is a dedicated inhibitor of Dpp signaling in flies and frogs. III. Identify enhancer element(s) directing sog expression during embryonic and adult development. IV. Determine whether a Sog protein(s) is secreted, diffuses, and binds to Dpp.

在这个建议中，我们描述了实验，以扩展我们以前的分析 编码泛神经转录因子的scratch（scratch）基因 可能作为非神经元基因表达的阻遏物发挥作用 （具体目标1）。我们还建议采取新的调查路线 重点分析了短原肠胚形成（sog）基因， 在我们研究泛神经增强子的过程中分离出来的。SOG 在早期神经外胚层中表达，并编码可能的拮抗剂， TGF β样Dpp信号通路（特异性目的II-IV）。 Sog和Dpp信号通路在人类发育过程中是高度保守的。 进化DPP及其脊椎动物同源物BMP-4可以在功能上 在果蝇的背腹图案形成中相互替代， 在脊椎动物的骨形态发生中。此外，非洲爪蟾的同源物 最近已经鉴定出了被称为弦蛋白的SOG。像sog和民进党在 果蝇、脊索蛋白和BMP-4也对背腹侧 模式化因此，sog、/chordin和dpp/BMP-4基因很可能是 在无脊椎动物的早期背腹模式中扮演保守的角色 和脊椎动物 因此，这些研究与以下方面高度相关： 了解TGF β超家族中生长因子的调节。 具体的研究目标是： I.确定泛神经基因scratch和deadpan如何合作， 促进神经发生。 二.确定sog是否是Dpp信号传导的专用抑制剂， 苍蝇和青蛙 三.鉴定在细胞周期中指导sog表达的增强子元件 胚胎和成人发育。 四.确定Sog蛋白是否分泌、扩散和结合 民进党