Analysis of Flexo/lft88, a novel regulator of Hh pathway

描述（由申请人提供）：该项目的目标是解决Flexo蛋白在Hedgehog （Hh）信号通路中的功能。Flexo是一种enu诱导的小鼠突变体，在多个组织中显示Hh信号受损，并与Polaris（一种与细胞内运输蛋白同源的蛋白）等位。在这个项目中，突变的分子性质和包括脑、脊髓和肢体在内的多个组织的缺陷将被详细表征。Flexo突变细胞产生或响应Hh信号的能力将通过体外细胞培养和体内组织和蛋白浸泡头移植来确定。将进行上位分析，以确定Flexo和Hh信号组件（如Ptc1和Gli3）之间的遗传关系。最后，Flexo的亚细胞定位和Flexo与其他Hh通路组分之间的物理相互作用将被检查

DESCRIPTION (provided by applicant): The goal of this project is to address the function of Flexo protein in the Hedgehog (Hh) signaling pathway. Flexo, an ENU-induced mouse mutant, shows compromised Hh signaling in multiple tissues and is allelic to Polaris, a protein with homology to intracellular transport proteins. In this project, the molecular nature of the mutation and the defects of multiple tissues including the brain, spinal cord and limb will be characterized in detail. The ability of Flexo mutant cells to produce or respond to Hh signals will be determined by both in vitro cell culture and in vivo tissue and protein-soaked bead transplantation. Epistatic analyses will be performed to determine the genetic relationships between Flexo and Hh signaling components such as Ptc1 and Gli3. Finally, the subcellular localization of Flexo and the physical interactions between Flexo and other Hh pathway components will be examined