Researchers reveal important gene in early cilia development

The primary cilium is a microtubule-based organelle with important sensory and signaling functions. These specialized extensions transduce mechanical and chemical stimuli to support cellular functions, such as organogenesis and tissue homeostasis, and the absence or malfunction of primary cilia underlies numerous human diseases, known as ciliopathies.
Considering the demonstrated importance of cilia for human health, many research groups have sought to characterize the molecular mechanisms of cilia biogenesis and function. Recently, researchers at the National Eye Institute identified a gene that plays an important role in cilia development.
Patients with ciliopathies experience a range of effects, and some ciliopathies are fatal. Bardet-Biedl and Joubert syndromes, for example, result in deafness, retinal degeneration and kidney disease. Meckel syndrome, meanwhile, is a severe ciliopathy, and most people afflicted by it die before or shortly after birth due to respiratory problems or kidney failure.
Image courtesy of Shobi Veleri and previously published in Nature Communications
In post-mitotic cells, the primary cilium originates from the mother centriole, which functions as a basal body. The mother centriole also contains distal and subdistal appendages that are important for membrane tethering and docking.
The NEI researchers, led by Anand Swaroop, zeroed in on the gene Cc2d2a, mutations in which are associated with Meckel syndrome.
The team generated a Cc2d2a-null allele in mice. Loss of Cc2d2a resulted in embryonic lethality with defects in multiple organs associated with cilia biogenesis, consistent with Meckel syndrome phenotypes. Cilia were absent in the tissues of mutant mice during early stages of development, and there was neither subdistal assembly nor microtubule anchoring.
The researchers say the work, published in the journal Nature, demonstrates an essential role for CC2D2A in the formation and/or stabilization of subdistal appendages to initiate the process of cilia biogenesis. The findings are of clinical and biological significance, as they begin to elucidate the molecular basis of the Cc2d2a mutations present in Meckel syndrome.
Elizabeth MeierElizabeth Meier ( is a third-year Ph.D. student at Johns Hopkins School of Medicine, where she studies bacterial cell division in Erin Goley's lab. Originally from Portland, Ore., she completed her undergraduate studies at Scripps College, a small liberal arts college in Southern California. There, she minored in Latin American studies and majored in biology. She would love to find a career that integrates both her humanities and science backgrounds.