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

描述（由申请人提供）：本项目的目标是解决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，在多种组织中显示出受损的Hh信号传导，并且与Polaris等位，Polaris是一种与细胞内转运蛋白具有同源性的蛋白质。在这个项目中，突变的分子性质和包括大脑，脊髓和肢体在内的多种组织的缺陷将被详细描述。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质浸泡的珠移植来确定。将进行上位性分析，以确定Flexo和Hh信号传导组分（如Ptc1和Gli3）之间的遗传关系。最后，将研究Flexo的亚细胞定位以及Flexo与其他Hh通路组分之间的物理相互作用

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