Analysis of Hedgehog Signaling in Mouse Intraflagellar Transport Mutants

Intraflagellar transport (IFT) has been studied for decades in model systems such as Chlamydomonas and Caenorhabditis elegans. More recently, IFT has been investigated using genetic approaches in mammals using the mouse as a model system. Through such studies, a new appreciation of the importance of IFT and cilia in mammalian signal transduction has emerged. Specifically, IFT has been shown to play a key role in controlling signaling by Sonic and Indian Hedgehog (Hh) ligands. The effects of mutations in IFT components on Sonic Hh signaling in the embryo are complex and differ depending on the nature of the components, alleles, and tissues examined. For this reason, we provide a basis for analyzing the phenotype as a guide for those investigators who study IFT in cell culture or use invertebrate systems and wish to extend their studies to include development of the mouse embryo. We provide an overview of Sonic Hh-dependent tissue patterning in the developing neural tube and limb buds, the two systems in which it has been studied most extensively, and we show examples of how this patterning is disrupted by mutations in mouse IFT components. I