Mechanisms of mammalian ciliary motility: Insights from primary ciliary dyskinesia genetics

Sperm-Associated Antigen–17 Gene Is Essential for Motile Cilia Function and Neonatal Survival

“…Although most of the knockout mice that developed hydrocephalus died, the ventricular dilatation was modest, and mice with more severe degrees of hydrocephalus (such as the mixed background SPAG6-deficient mice we previously created) survive for a week or two after birth (12). The axoneme CP is involved in the control of ciliary and flagellar waveforms (2). Although the basic axonemal structure is highly conserved across species, cilia and flagella perform specialized functions unique to the tissue or cell in which they are present.…”

“…Primary ciliary dyskinesia (PCD), which results from defects in the formation and function of cilia and flagella, is a relatively rare disorder affecting 1 in 16,000 individuals worldwide (2). The axoneme, the highly conserved cytoskeletal structure of motile cilia, has a "9 1 2" arrangement consisting of nine outer doublet microtubules surrounding a central microtubule pair.…”

“…The sliding of the outer doublet microtubules is modulated by the central pair (CP) apparatus (2)(3)(4). The two microtubules in the CP are structurally and biochemically dimorphic, and by convention receive separate designations (e.g., C1 and C2).…”

The primary cilium

“…[6][7][8]11,19 This "9+2" arrangement (as opposed to the "9+0" of primary cilia), together with the presence of specialized ciliary motors and accessory proteins, provide motile cilia with the capacity to actively bend and thereby undergo coordinated beating patterns that create flow over the cell surface. Motile cilia are often longer than primary cilia and present in multiple copies, such as those found on the epithelial surface of the respiratory tract or oviduct, or the ventricular ependyma in the brain.…”

“…Loss of motility of the respiratory multiciliated epithelia, for example, gives rise to primary ciliary dyskinesis (PCD) or immotile ciliary syndromes, such as Kartegener's Syndrome, that lead to persistent respiratory infections. 19 The presence of motile cilia in the oviduct and brain, as well as the central role that the flagellum plays in sperm motility, also provide an explanation for why ciliary defects cause infertility and certain neurological diseases, such as hydrocephalus. Moreover, it is possible to understand from a mechanical perspective why loss of nodal cilia function leads to laterality defects in terms of body patterning, such as heterotaxy, situs ambiguous, and situs inversus.…”