Review
Neuronal primary cilia: a review

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Abstract

Primary cilia in neurons have often been regarded as rare, vestigial curiosities. However, neuronal cilia are now gaining recognition as ubiquitous organelles in the mammalian brain, raising speculation about what their functions may be. They might have some features tailored for the nervous system and others that serve needs shared by a spectrum of other cell types. Here we review clues from the literature and present new data supporting several possibilities for the significance of neuronal cilia. Our immunocytochemical results show regional heterogeneity in neuronal cilia. Brain regions nearer to the cerebral ventricles had longer cilia, suggesting that they might sense chemicals such as peptides, originating from cerebrospinal fluid. In mutant Tg737orpkmice, most brain regions appeared to be missing cilia. The importance of intraflagellar transport proteins establishes a functional link between neuronal cilia and other primary cilia.

Section snippets

The long history of the discovery of neuronal cilia

Most neuroscientists would be surprised—if not downright skeptical—to hear that primary cilia are a consistent feature of neurons in the mammalian central nervous system. Over a century ago, the preeminent neuroanatomist Ramón y Cajal (Ramón y Cajal, 1995) drew and described in meticulous detail a myriad of neurons without including primary cilia, so how could neurons have them? To this day, cilia are rarely catalogued among the organelles of neurons, despite several demonstrations of their

Not all neuronal cilia are alike: regional variations in function?

We observed that for nearly all regions of the rat CNS, each neuron appears to have a solitary cilium(Fig. 1) as visualized by distinctive staining with an antibody raised to an N-terminal peptide from subunit of mouse G11 (Santa Cruz Biotechnology, Santa Cruz, CA, USA) (Fuchs et al., 2000; Hughes et al., 2002), which is the α-subunit of G11, a G protein that couples many neurotransmitter receptors to their second messenger responses. Staining in cilia was completely abolished by preabsorption

Information from sensory cilia

Specialized sensory cilia convey a large portion of the stream of information to the vertebrate brain. These cilia are typically nonmotile and are thought to be derived from primary cilia (Dubruille et al., 2002; Menco and Farbman, 1985a). Olfactory cilia are endowed with a sensory transduction kit complete with olfactory receptors, G proteins, adenylyl cyclase, and ion channels that initiate depolarization of the ciliated olfactory neuron. Sensory neurons in acoustico-vestibular systems have

Primary cilia as responders

Sensing in cilia is useful insofar as the end result is an adaptive response. The cilia of sensory cells transduce stimulus energy into changes in ion permeability, which in turn translates as changes in membrane potential. But how can a tiny cilium get the attention of a large neuron? Based on the information that olfactory cilia—an average of 11 per neuron in rat (Menco and Farbman, 1985b)—can trigger action potentials in an olfactory receptor neuron, it seems likely that a single primary

Cilia in development

The relationship between cilia and cell proliferation is a topic of long-standing interest (Fonte et al., 1971; Ho and Tucker, 1989). Cilia emerge from basal bodies, which originate as centrosomes, which in turn organize the mitotic spindle. Precursor cells resorb cilia just before mitosis and regrow them afterwards. It is tempting to consider that cilia may mediate influences from the extracellular milieu on cell proliferation and differentiation. Ca2+levels are implicated in mediating many

Neuronal cilia depend on intraflagellar transport; clinical implications

We recently found that most neuronal cilia appeared to be absent in mutant Tg737orpkmice, suggesting that the intraflagellar transport protein polaris (IFT88), which is necessary for ciliogenesis in various cell types (Pazour et al., 2000; Yoder et al., 2002), is also important for neuronal cilia. Again, heterogeneity is evidenced by the observation that while many brain regions in IFT88-deficient mice lacked sst3-immunoreactive cilia, some brain regions retained shortened cilia, including much

Acknowledgements

We thank our students who participated in the research, particularly Rhome Hughes for his morphometric study of neuronal cilia. Those currently working on the Tg737orpkmouse brains include Ankur Patel, Rajin Shahriar, Suman Pasapuleti, and Weilan Zuo. We are grateful to Dr Gregory Pazour for providing the Tg737orpkbrains. This research was supported by NIMH MH41865 (JLF), NIH NS41891 (HDS), and grants from the University of North Texas.

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