| The PI's | Home | Ciliaffiliates | The Labs | Publications |
|
Almost every neuron has a single primary cilium
extending from its cell body. Like
primary cilia in other vertebrate cell types, these organelles are nonmotile
and have a backbone of 9 microtubule doublets. Most neuroscientists are not yet aware that
neurons have cilia, and little is known about their function. It is now known that primary cilia are
necessary for our very existence.
Without primary cilia in the embryonic node, vertebrates die early in
development. Individual organs such as the
kidney are severely defective if their primary cilia are missing. Our mission is to determine what primary
cilia do in the nervous system. We are
using three approaches:
1. Identification of receptors and other constituents of neuronal cilia. We are using immunohistochemistry to identify chemical and morphological clues to the function of cilia. We are particularly interested in identifying them cilia in human brain tissue, in order to investigate their involvement in neurological symptoms associated with ciliary diseases. 2. Mutant mice with defective neuronal cilia. We found that neuronal cilia become progressively shortened or disappear in the Tg737orpk mouse, which is a widely used mouse model of polycystic kidney disease. In conditional mutants that lack cilia in regions of the developing nervous system, we find that neural progenitor cells cannot receive their signals to proliferate, resulting in severely hypomorphic brain regions. We are using these mouse models to further investigate the function of cilia in neurons and neuronal precursors. 3. Neuronal cilia in vitro. We are learning how ciliogenesis is influenced by differentiation factors present in the culture medium, and are studying how cilia transduce signals. Based on the observations we have made thus far, we propose that neuronal cilia are functional extensions of an ancient system for sampling the internal milieu. Neuronal cilia are longer in brain regions closest to the brain ventricles, and they have receptors for substances that can reach the brain from the ventricular cerebrospinal fluid. Neural progenitor cells use these signals to regulate cell division. |
| Primary cilia in the nervous system are found on glia as well as neurons. We and others have identified primary cilia in the dorsal root ganglia of rats and mice, and many of these appear to be on the satellite glial cells that surround neurons. A number of complex interactions between neurons and satellite glial cells have been identified, but the picture is far from complete. For example, painful stimuli can evoke a dramatic response in satellite glial cells, which may in turn contribute to some of the longer-lasting effects of pain. We are currently conducting experiments to determine what role, if any, primary cilia may play in this response to pain. |