Function of FGFR signaling in positioning and detachment of buds (autotomy) in Hydra

FGFR 信号在水螅芽定位和分离（自切）中的功能

• 批准号: 200124234
• 负责人: Professorin Dr. Monika Hassel
• 金额: --
• 依托单位: Arbeitsgruppe Morphologie und Evolution der Wirbellosen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/200124234?language=en
• 关键词: Function; FGFR; signaling; positioning; detachment

We showed previously that in Hydra a single fibroblast growth factor receptor (FGFR), Kringelchen, controls detachment of asexually growing buds. Why Kringelchen mRNA is dynamically expressed also in early phases of budding remained open. Recently established, stably transgenic lines developed strong phenotypes: constitutive Kringelchen overexpression induces autotomy of the body column. Buds carrying a putatively dominant-negative variant fail to detach despite having formed an apparently normal foot. In both, synchronous budding occurs, indicating a role of the extracellular domain of FGFR in bud positioning. Our aim is to identify the molecular players and pathways targeted by Kringelchen, which control synchronous budding, detachment and autotomy. (i) The properties of the transgenic tissue will be investigated e.g. by transplantations and marker gene analysis. (ii) A potential FGF ligand will be characterized by binding- and bioassays. (iii) We will isolate downstream coupling proteins (FRS2, Dof) and elucidate by pharmacological inhibition and expression analysis which signaling elements are used to establish positive or negative feedback loops (PI-PKC, PI3-kinase, Ras/MAPK; Sprouty, Sef). Our study will help to understand the role of FGFR in bud positioning and instruction of tissue at the bud base.

我们以前曾证明，在九头蛇中，一种单一的成纤维细胞生长因子受体(FGFR)Kringelchen控制着无性生长的芽的脱落。为什么Kringelchen的mRNA也在萌芽的早期动态表达，这一点仍然是未知的。最近建立的稳定转基因株系发展出了强大的表型：结构性Kringelchen过度表达导致体柱自切。携带一种假定为显性-负性变异的芽，尽管已经形成了一个明显正常的脚，但仍然无法分离。在这两种情况下，都发生了同步发芽，表明FGFR的胞外结构域在芽定位中发挥了作用。我们的目标是确定Kringelchen所针对的分子成员和途径，它们控制着同步萌发、脱离和自切。(I)将通过移植和标记基因分析等方式研究转基因组织的特性。(Ii)潜在的成纤维细胞生长因子配体将通过结合试验和生物测定进行表征。(Iii)我们将分离下游偶联蛋白(FRS2、DOF)，并通过药理抑制和表达分析阐明哪些信号元件用于建立正反馈环或负反馈环(PI-PKC、PI3-K、RAS/MAPK；Sprouty、Sef)。我们的研究将有助于理解FGFR在芽的定位和芽基组织的指导中的作用。