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,
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 where 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
- How do cilia interpret signals essential to
- Do cilia participate in Hedgehog-mediated
- How do cells regulate whether they form a cilium?
- How do differences in cilia structure and composition affect function among different types of cilia? We are using cultured mouse tracheal epithelial cells mTECs as one way to address this question. Check out a video here.
- 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.