MOLECULAR GENETICS OF EARLY NEUROGENESIS

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

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.