MOLECULAR GENETICS OF EARLY NEUROGENESIS

在这个提案中，我们描述了扩展我们先前分析的实验 Scratch(SCRT)基因编码泛神经转录因子 可能作为非神经元基因表达的抑制因子发挥作用 (具体目标L)。我们还建议遵循一条新的调查路线 重点分析了短肠原肠形成(Sog)基因，我们发现 在我们研究泛神经增强剂分子的过程中分离出来的。SOG 在早期的神经外胚层中表达，编码可能的拮抗剂 TGFbeta样DPP信号通路(特异性AIMS II-IV)。 SOG和DPP信号通路在 进化论。DPP及其脊椎动物同源物BMP-4可以在功能上 苍蝇背腹纹形成过程中的相互替代 脊椎动物的骨形态发生。此外，非洲爪哇的同源物 被称为Chordin的SOG最近被发现。就像SOG和DPP一样 苍蝇、脊索素和BMP-4对腹背侧部也有相反的影响 图案化。因此，SOG、/Chordin和DPP/BMP-4基因很可能 在无脊椎动物早期背腹模式中发挥保守作用 和脊椎动物。因此，这些研究与以下方面高度相关 了解生长因子在转化生长因子β超家族中的调控。 具体的研究目标是： I.确定泛神经基因抓挠和面无表情如何协作 促进神经再生。 Ii.确定SOG是否是DPP信号的专用抑制剂 苍蝇和青蛙。 确定调控SOG表达的增强子元件(S) 胚胎和成体发育。 确定SOG蛋白(S)是否分泌、扩散和结合到 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.