Cilia Structure and Function in Human Disease

Abstract

Ciliary dysfunction causes a large group of developmental and degenerative human diseases known as ciliopathies. These diseases reflect the critical roles that cilia play in sensing the environment and in force generation for motility. Sensory functions include our senses of vision and olfaction. In addition, primary and motile cilia throughout our body monitor the environment allowing cells to coordinate their biology with the cells around them. This coordination is critical to organ development and maintenance, and ciliary dysfunction causes diverse structural birth defects and degenerative diseases. Defects in motility cause lung disease due to the failure of mucociliary clearance, male infertility due to the failure of sperm motility and the ability of sperm to move through the efferent ducts, and disturbances of the left-right axis due to a failure of nodal cilia to establish proper left-right cues.

Figure 1.

Cilia Structure A. Structure of a typical mammalian cilium. B. Cross sections through the cilium at the levels marked a, b, and c. Ba shows a cross section through a motile 9+2 cilium on the left and a non-motile 9+0 on the right.

Figure 2.

Mammalian Cilia Diversity. Mammalian cells express a variety of cilia to serve diverse sensory and motile functions. All cilia contain a microtubule-based cytoskeleton or axoneme enclosed by membrane (blue). Primary and olfactory cilia share similar axonemal structure with a transition zone at the base (a) followed by a 9+0 (b) cytoskeleton that gradually loses microtubules as it extends distally (c). Photoreceptor cilia have an extended transition zone called the connecting cilium (a). The 9+0 arrangement is lost as the axoneme extends along the photoreceptor disks (green) in the outer segment (c). Kinocilia extend from the side of an array of microvilli known as stereocilia (green). Structurally, kinocilia contain axonemal structures found in motile cilia including the central apparatus, outer dynein arms and radial spokes. Stereocilia have an actin-based cytoskeleton and are not cilia. Motile cilia have a transition zone (a) and a well-defined 9+2 cytoskeleton with a central apparatus, radial spokes, and dynein arms. Sperm flagella share features with motile cilia but have accessory structures. In the midpiece, each outer doublet is associated with an outer dense fiber (black) that is wrapped with a layer of mitochondria (green). The outer dense fibers extend through the tail to almost the tip (c). The outer dense fibers distal to the midpiece are wrapped with a fibrous sheath (red)