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

我们先前表明，在九头蛇中，单一的成纤维细胞生长因子受体（FGFR） Kringelchen控制无性生长芽的脱离。为什么Kringelchen mRNA在出芽早期也动态表达，保持开放。最近建立的，稳定的转基因系发展出强大的表型：组成型Kringelchen过表达诱导体柱自切。芽携带推定的显性阴性变异不能分离，尽管已经形成一个明显的正常足。在这两种情况下，同步出芽发生，表明FGFR的细胞外结构域在芽定位中的作用。我们的目的是确定Kringelchen靶向的分子参与者和途径，控制同步出芽，脱离和自切。(i)转基因组织的特性将被研究，例如通过移植和标记基因分析。（ii）潜在的FGF配体将通过结合和生物测定来表征。（iii）我们将分离下游偶联蛋白（FRS2, Dof），并通过药理学抑制和表达分析阐明哪些信号元件用于建立正反馈或负反馈回路（PI-PKC, PI3-kinase, Ras/MAPK; Sprouty, Sef）。我们的研究将有助于了解FGFR在芽定位和芽基部组织指导中的作用。

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.