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Cilia and flagella are hair-like filamentous organelles that have been evolutionarily conserved across the eukaryotes. Our high school biology lectures have taught us how protozoans, like Paramecium, use beating cilia to swim around in water. 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. 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. In addition, almost every vertebrate cell 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 signalling pathways that operate during embryonic development and in adult physiology. Our interest in cilia largely stems from the fact that a significant number of human diseases, collectively called ciliopathies, have been associated with dysfunction of these organelles.
In my talk, I shall describe our work on the function of the transcriptional regulator Foxj1 in programming the biogenesis of motile cilia. Then, I shall illustrate how two target genes of Foxj1 that we have recently discovered is providing us with new insights into the function and differentiation of two distinct kinds of cilia. The first gene, Ccdc11, is required for the movement of mono motile cilia in the embryonic node. Patients with mutations in CCDC11 develop congenital heart disease because of improper activation of the genetic pathway that determines the sidedness of our organ systems. The second gene GMNC has a completely different role in activating the gene expression program for making multiciliated cells, which have a specialized armoury of hundreds of motile cilia for mucus clearance in our respiratory tracts. Defective formation of these multiciliated cells is associated with severe respiratory disorders that typically culminate in irreparable lung damage.
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