Cilia have diverse functions at the interface between the cell and the extracellular space. Cilia are large complex organelles composed of the ciliary axoneme surrounded by the ciliary membrane. The axoneme is comprised of 9 microtubule doublets and attached motor and transport proteins. Many cells have a single cilium that arises from the centriole (a monocilium). By displaying a variety of receptors, these “signaling” cilia are adapted to function as “cellular antennae”, reaching out beyond the cell surface to capture a variety of signals. Monocilia are created and resorbed in a cell-cycle dependent manner, predicting a central role in cell cycle regulation. Mechanisms that contribute to the biogenesis and resorption of cilia remain ill defined.
In motile cilia, such as on the multiciliated epidermis (trachea, oviduct, or Xenopus tadpole skin), dynein motors generate ciliary movement, which drives fluid flow. In the Left-Right Organizer (LRO), this fluid flow is the initiating event in the LR signaling cascade, and is essential for proper cardiac looping and heart development. Defects in the structure and function of cilia are the cause of many diseases, collectively referred to as the ciliopathies. These include heterotaxy, but can also lead to blindness, deafness, pulmonary infections, infertility, and kidney disorders as well as others. In our analysis of patients with congenital malformations, we have identified a number of genes that affect cilia. Some of them act directly on the cilium, while others act indirectly to change cilia types or downstream signaling.
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