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First published online 4 October 2006
doi: 10.1242/dev.02595

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The roles of cilia in developmental disorders and disease

Huntsman Cancer Institute Center for Children, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.

View larger version (56K): [in a new window]   Fig. 1. Cilia structure and intraflagellar transport. (A) A typical cilium consists of an axoneme of nine doublet microtubules (two are shown in B). Each doublet arises from the inner two microtubules of the basal body microtubule triplets. The axoneme is surrounded by a specialized ciliary membrane that is separated from the cell membrane by a zone of transition fibers. (B) A cross-section of 9+2 and 9+0 cilium. Cilia are broadly divided into two types based on the presence or absence of a central pair of microtubule singlets in the axoneme (9+2 or 9+0 structure, respectively). Inner and outer dynein arms, which are usually associated with 9+2 cilia, can be present in either type of cilium and are important for ciliary motility. Ciliary assembly and maintenance is accomplished by intraflagellar transport (IFT), which relies on the microtubule motor proteins kinesin 2 and cytoplasmic dynein to transport IFT protein complexes and their associated cargo up and down the length of the cilium (depicted in A). Abbreviations: Eb1, end-binding protein 1; Pc1 and Pc2, polycystin 1 and polycystin 2.

View larger version (13K): [in a new window]   Fig. 2. Primary cilia in the embryonic node and left-right axis specification. The illustration represents the ventral surface of the mouse embryonic node, viewed from the center of the node toward the left. Motile cilia (green) in the center of the node rotate in a clockwise direction. Because the cilia are positioned at an angle at the posterior end of the node cells, when clockwise-rotating cilia stroke toward the right they are close to the cell surface and flow is impeded; when they stroke to the left at the top of the arc, they are away from the cell surface and flow is unimpeded. This produces an asymmetric flow of fluid (red arrows) towards the left periphery of the node. At the left periphery of the node, fluid flow is sensed by mechanosensory cilia (blue), and/or secreted signaling molecules are concentrated by the flow and received by chemosensory cilia. These events, alone or in combination, cause intracellular Ca2+ levels to increase in cells on the left side of the node, which triggers a signal transduction pathway that controls the asymmetric expression of genes that establish the left-right axis. A, anterior; L, left; P, posterior; R, right.

View larger version (42K): [in a new window]   Fig. 3. Functions of primary cilia. The primary cilium acts as a sensory organelle that transfers information from the extracellular environment to the cell interior. For example, cation channels composed of the polycystin proteins Pc1and Pc2 in the ciliary membrane sense mechanical stress, while receptors such as the platelet-derived growth factor receptor (Pdgfr) sense extracellular ligands. The processing and transfer of signaling information to the cell is mediated by specialized proteins, including smoothened (Smo), and several microtubule-associated protein complexes that include members of the nephronophthisis protein family [Nphp, inversin (Invs)], and proteins associated with Bardet-Biedl syndrome (BBS). Signals from primary cilia ultimately are involved in regulating crucial cellular processes, including the cell cycle, cytoskeletal organization, intraflagellar transport and signaling pathways, such as the hedgehog, canonical Wnt and non-canonical Wnt/planar cell polarity (PCP) pathways. Abbreviations: Apc2, anaphase promoting complex protein 2; Dvl1, dishevelled; Nek8, NIMA-related kinase 8; Ofd1, oral-facial-digital type 1 protein; Pcm1, pericentriolar material protein 1.