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

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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