In the vertebrate nervous system, the primary cilium is increasingly viewed as hub for certain neural developmental signaling pathways, and growing data suggest that this is also true for several types of adult neuronal signaling. AZD6244 supplier To set the stage for understanding the functions of primary cilia in the CNS, particularly for readers new

to cilia research, we begin with a summary of basic cilia biology, and a brief appraisal of the range of physiological defects that arise in mice and humans from cilia dysfunction. The primary cilium is a slender protrusion of the cell membrane about 1–5 microns in length. The ciliary membrane surrounds an axoneme, composed of nine microtubule pairs. These are anchored to a microtubule organizer, the ciliary basal body, which is a modified mother centriole. Appropriate to an organelle that propagates specialized signals, the primary cilium is partially isolated

from the rest of the cell by a transition INCB018424 zone at its base, which acts as a ciliary pore and a docking area for proteins headed for the cilium (Rosenbaum and Witman, 2002, Pedersen and Rosenbaum, 2008, Satir and Christensen, 2008, Seeley and Nachury, 2010 and Sorokin, 1968). Proteins selected for entry (Emmer et al., 2010 and Inglis et al., 2006) are carried along the ciliary axoneme by intraflagellar transport (IFT) (Figure 1), first discovered in the flagella of the alga Chlamydomonas reinhardtii ( Kozminski et al., 1993 and Kozminski et al., 1995). Cilia membrane proteins needed for signaling and are prevented from leaving the cilium prematurely by a septin diffusion barrier at the base of the primary cilium, below the site at which proteins are first inserted into the ciliary membrane ( Hu et al., 2010). A similar diffusion barrier is formed in budding yeast, supporting an evolutionarily conserved role for septins in maintaining separate cell compartments ( Hu et al., 2010). Secondary cilia, which include eukaryotic flagella, differ from primary cilia in that the axoneme contains an extra central pair of microtubules, linked by radial spokes to the nine outer microtubule

pairs that are attached to a dynein motor that drives microtubule sliding and generates movement (Pedersen and Rosenbaum, 2008, Rosenbaum and Witman, 2002 and Satir and Christensen, 2008) (Figure 2A). Secondary cilia are therefore motile, whereas primary cilia are generally not. Additionally, a cell possesses a single primary cilium but may have many secondary cilia. In the CNS, the multiciliated epithelial cells lining the ventricles are tufted with secondary cilia that sway in synchrony to move cerebrospinal fluid (Banizs et al., 2005 and Dalen et al., 1971) (Figure 2A). Specialized sensory cilia in the nervous system are found between the outer and inner segments (OS, IS) of retinal photoreceptors (Figure 2B), and on the dendrites of olfactory receptor neurons (ORNs) (Figure 2C).