Cilia, Wnt signaling, and the cytoskeleton

The primary cilium had long been ignored by biologists and was considered to be a vestigial remnant of evolution, similar to the human appendix. However, a growing number of human disorders are being attributed to dysfunctions in cilia or cilia-related proteins [1], leading to the term ciliopathies to describe these disorders. Ciliopathies display high degrees of clinical variability, genetic heterogeneity, and phenotypic overlap [2], complicating their discovery and diagnosis. But, in recent years an explosion of data has linked the cilium to several crucial cellular processes and various signaling pathways. Initially cilia were classified as either motile or primary cilia based on their internal structure. Motile cilia were thought to be comprised exclusively of nine outer microtubule doublets with a central pair of microtubules (9+2). In contrast, primary cilia (also referred to as sensory cilia) lack the central microtubule doublets (9+0). Motile cilia are known to be required for mucus clearance, cerebrospinal fluid flow, sperm motility, and leftward flow at the embryonic node, among other functions [3], and defects in this motility are known to be associated with diseases such as Kartagener syndrome (primary ciliary dyskinesia). Primary cilia, in contrast, while expressed on virtually every cell, were considered to be non-functional, evolutionary remnants.More recently, the primary ciliary membrane has been shown to be rich in various channels and receptors [4,5], suggesting that the cilium may serve as the signaling antenna for the cell. In this capacity, cilia might sense developmental morphogens, growth factors, hormones, odorants, and other extracellular signals. Moreover, the cilia-associated basal body complex appears to serve as a gatekeeper for the regulation of downstream intracellular signaling events that are initiated as a result of ciliary receptor activation. As the cilium has no protein synthetic machinery of its own, all the components required