Structure-function analysis of the mouse Delta1 gene in vivo and in vitro

小鼠Delta1基因体内外结构功能分析

• 批准号: 35019200
• 负责人: Professor Dr. Achim Gossler
• 金额: --
• 依托单位: Institut für Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35019200?language=en
• 关键词: Structure; function; analysis; mouse; Delta1

Notch signalling is pivotal for the regulation of multiple developmental processes. Notch genes encode transmembrane proteins that act as receptors for Delta and Serrate proteins. These interactions are mediated and modulated by multiple EGF-like repeat modules in the extracellular domains of these proteins. To analyze the significance of particular EGF-like repeats of the mouse Notch ligand Delta1 (Dll1) for the outcome of Notch signalling in vivo we have generated an allelic series of Dll1, in which each of the eight EGF repeats has been mutated individually by replacing conserved Cysteine residues by Glycine. These mutations show a broad spectrum of phenotypic variation, indicating that individual EGF repeats in DLL1 are not equivalent with respect to Notch activation in vivo. The proposed experiments aim at defining the processes affected by individual EGF repeat mutations, and the properties of DLL1 variants with respect to receptor binding and activation in vivo and in vitro. This study will provide insights into the role of particular EGF-like repeats of DLL1 in different developmental contexts during mouse embryogeneis and define regions of DLL1 mediating Notch binding and activation.

缺口信号对多种发育过程的调控起着关键作用。Noch基因编码跨膜蛋白，作为Delta和Serrate蛋白的受体。这些相互作用是由这些蛋白质胞外区的多个EGF样重复模块介导和调节的。为了分析小鼠Notch配体Delta1(Dll1)特定的EGF样重复对体内Notch信号转导结果的意义，我们产生了Dll1的等位基因系列，其中八个EGF重复序列中的每一个都通过用甘氨酸取代保守的半胱氨酸残基而单独突变。这些突变表现出广泛的表型变异，表明DLL1中的单个EGF重复序列与体内的Notch激活并不等同。拟议的实验旨在确定单个EGF重复突变影响的过程，以及DLL1变体在体内和体外与受体结合和激活的特性。这项研究将深入了解DLL1特定的EGF样重复序列在小鼠胚胎发育过程中的不同发育环境中的作用，并确定DLL1介导Notch结合和激活的区域。

项目成果

S/T Phosphorylation of DLL1 Is Required for Full Ligand Activity In Vitro but Dispensable for DLL1 Function In Vivo during Embryonic Patterning and Marginal Zone B Cell Development

• DOI: 10.1128/mcb.00965-13
• 发表时间: 2014-04-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Braune, Eike-Benjamin;Schuster-Gossler, Karin;Gossler, Achim
• 通讯作者: Gossler, Achim