Cilia and Human Disease

Abstract

Cilia and centrioles are highly conserved organelles that have hundreds of proteins associated with them. Studies in mice have shown that these organelles are essential for mammalian development and mice that cannot assemble them die in utero . However, mutations in many cilia and centriole genes cause human diseases that show a great range in defects. Defects in centrioles are associated with microcephaly and mental retardation. The reduction in brain size is related to the loss of neuronal progenitor cells. Defects in centrioles may also be associated with Sjögren syndrome, an autoimmune disease, because of defects in formation of the immunological synapse. Defects that cause immotile cilia result in chronic respiratory infections, infertility, and congenital heart defects. Defects in primary cilia share various symptoms that include loss of vision, obesity, diabetes, cystic kidney disease, mental retardation, polydactyly, and short bones. Many of these diseases are associated with the transport and sorting of receptors onto the ciliary membrane for sensing the environment. Key Concepts: Cilia perform functions in many different tissues and during development. Many ciliary mutations affect multiple tissues and organs. Key signalling pathways require cilia. Orientation of the spindle during mitosis requires functional centrioles.

Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and proper morphology of inner dynein arms

“…Motile cilia (also known as flagella) are antenna-like organelles protruding from many types of cells and required for motility and cell signaling [ 1 , 2 ]. Motile cilia are essential for normal vertebrate development, fertility, and organ homeostasis [ 3 – 7 ]. The movement of motile cilia is driven by the ciliary dynein motors, which are composed of outer (ODA) and inner dynein arms (IDA) [ 8 – 10 ].…”

A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles

“…The best-known case certainly is mucociliary clearance of the airway epithelia, which constitutes a first-line defense mechanism against pathogens. Patients suffering from impaired mucus production or cilia function show a high prevalence of lung infections (Albee and Dutcher, 2012;Cowan et al, 2001;Livraghi and Randell, 2007;Rubin, 2007). MCEs must be able to adapt to changing environmental conditions.…”

Identification of Cilia Genes That Affect Cell-Cycle Progression Using Whole-Genome Transcriptome Analysis in Chlamydomonas reinhardtti

“…In recent years, interest in cilia as an important organelle resurfaced due to a growing list of human diseases associated with ciliary defects, which cause a wide range of phenotypes that include renal cysts, liver disease, cognitive impairment, retinal degeneration, obesity, skeletal bone defects, laterality defects, and polydactyly (Albee and Dutcher 2012). Abnormal formation or function of these structures has been implicated as an underlying cause of many syndromes and disorders that have traditionally been recognized as disjoint conditions.…”