Eukaryotic cilia and flagella are cellular structures familiar to schoolchildren everywhere for the elegant swath they cut as they propel protozoa through pond water. Less well recognized is the fact that a single immotile cilium is present on almost every type of vertebrate cell. These so-called primary cilia were discovered more than a century ago and, yet, their functions remain largely unexplored (Singla and Reiter, 2006).

It is now becoming clear that the primary cilium plays important roles in both development and disease. Perhaps its most dramatic function is in the kidney ? ciliary defects cause polycystic kidney disease, the most common life-threatening monogenic illness. Primary cilia also have roles in sensing environmental information. Photoreceptors and odorant receptors function on primary cilia, and primary cilia are essential for sound reception. Therefore, it is not much of an exaggeration to say that we see, smell and hear through cilia.

Our work suggests that cilia also function as critical mediators of intercellular signals during development (Corbit et al., 2005; May et al., 2005; Reiter and Skarnes, 2006). One crucial role is in the coordination of the Hedgehog signal transduction pathway. Hedgehog signals are essential regulators of embryonic patterning and cell proliferation, and defects in Hedgehog signaling are important causes of both birth defects and many cancers. We are currently extending this work by asking a few fundamental questions about primary cilia:

• Do cilia transduce intercellular signals other than Hedgehog?
• How do cilia interpret signals essential to vertebrate development?
• Do cilia participate in Hedgehog-mediated oncogenesis?
• How do cells regulate whether they form a cilium?
• Sperm flagella are highly modified cilia. How are they built and what role have they played in human evolution?

This work has begun to suggest that the primary cilium is an organelle dedicated to signal transduction, somewhat analogous to a cellular antenna. We hope that our current endeavors will reveal how this antenna interprets the signals required for normal development and homeostasis, and how malfunctions in the antenna contribute to cancer and other important human diseases.

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