Modeling ciliopathies: Primary cilia in development and disease

Primary (nonmotile) cilia are currently enjoying a renaissance in light of novel ascribed functions ranging from mechanosensory to signal transduction. Their importance for key developmental pathways such as Sonic Hedgehog (Shh) and Wnt is beginning to emerge. The function of nodal cilia, for example, is vital for breaking early embryonic symmetry, Shh signaling is important for tissue morphogenesis and successful Wnt signaling for organ growth and differentiation. When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly. The etiology of several uncommon disorders has recently been associated with cilia dysfunction. The causative genes are often similar and their cognate proteins certainly share cellular locations and/or pathways. Animal models of ciliary gene ablation such as Ift88, Kif3a, and Bbs have been invaluable for understanding the broad function of the cilium. Herein, we describe the wealth of information derived from the study of the ciliopathies and their animal models.