Ciliopathies: an Update

Abstract

Cilia are hair-like organelles that extend from the surface of almost all human cells. Nine doublet microtubule pairs make up the core of each cilium, known as the axoneme. Cilia are classified as motile or immotile; non motile or primary cilia are involved in sensing the extracellular environment. These organelles mediate perception of chemo-, mechano- and osmosensations that are then transmitted into the cell via signaling pathways. They also play a crucial role in cellular functions including planar cell polarity, cell division, proliferation and apoptosis. Because of cilia are located on almost all polarized human cell types, cilia-related disorders, can affect many organs and systems. The ciliopathies comprise a group of genetically heterogeneous clinical entities due to the molecular complexity of the ciliary axoneme. Cilia are involved in left-right laterality in the embryo, mucociliary clearance, reproductive function, neuronal development, photoreception, olfaction, homeostasis or hormonal regulation. Ciliopathies can involve single organs or can occur as multisystem disorders with phenotypically variable and overlapping disease manifestations. However, the importance of the cilium’s role in the development of several diseases is still a matter of active research. In this review, we will define ciliary ultrastructure and function, the genetic complexity associated with ciliary dysfunction and clinical manifestations. Increasing knowledge of the role of cilia in morphogenesis pathways in conjunction with genetic studies is necessary to improve the characterization of this previously unconnected group of diseases.