Cilia and Ciliopathies

Cilia and flagella are microtubule based hair-like filamentous organelles that have been conserved evolutionarily in the eukaryotes. Our high school lectures have taught us how protozoans, like Paramecium, use beating cilia to swim around in water. We have also learnt that certain tissues in our own bodies have motile cilia. For instance, motile cilia that line the length of our respiratory tract beat to clear mucus that entangles pathogens and pollutants which enter through the nose as we breathe. Cilia also perform sensory functions. Besides locomotion, cilia in the protozoans are used for phototactic and chemotactic behavior. In the metazoans, many sense organs have cilia that have lost the motility apparatus and have become dedicated sensory organelles. Photoreceptors in the eye and olfactory neurons in the nose have such highly specialized sensory cilia. Several decades ago it was discovered that in the vertebrates, not just the sense organs, but almost every cell of the body differentiates a single immotile cilium at the end of cell division or after differentiation. Although regarded as vestigial structures for a long time, it has now become apparent that these so called primary cilia also function as hubs for a large number of signaling pathways that operate during embryonic development and in adult physiology. Given the manifold functions of cilia, it is unsurprising that a wide spectrum of human diseases, theciliopathies, arises from defects in cilia formation and function. In this seminar, I will discuss work done in my laboratory on the role of theciliary proteins Kif7 and Dzip1 and the transcription factor FoxJ1 in the biogenesis of primary and motile cilia. I will illustrate how our findings are leading to the discovery of genes mutated in ciliopathies.