Scanning electron microscope image of cilia projecting from lung trachea epithelium. [Charles Daghlian (Public domain), via Wikimedia Commons]
Scanning electron microscope image of cilia projecting from lung trachea epithelium. [Charles Daghlian (Public domain), via Wikimedia Commons]

As slender hair-like projections on many different cell types, cilium, a Latin word meaning eyelash, serve a much greater purpose than to accentuate the cell’s exterior aesthetics, as eyelashes often do for the face. Broken into two categories, cilia are either motile or non-motile—in the latter they typically act as sensory organelles and are referred to as primary cilia.

Mutations within the genes that constitute the two types of cilia can lead to a host of diseases affecting a wide array of diverse body systems such as the respiratory tract, kidneys, reproductive organs, and nervous system—the ciliopathies, as scientist often refer to them. Now, a huge collaboration of researchers from more than 40 institutions worldwide and led by investigators at the University of Leeds, have put together a comprehensive list of genes that are involved in defects of cilium biogenesis.

“This research gives us the best list yet of the human genes needed to make cilia,” explained senior author Colin Johnson, Ph.D., professor of medical and molecular genetics in the School of Medicine at the University of Leeds. “This is an important issue in biology, but it also directly benefits patients because we can find new genetic causes for ciliopathies. We've found some completely unexpected cell processes that are linked to these diseases which should help in the search for future treatments.”

The findings from this study were published recently in Nature Cell Biology through an article entitled “An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.”

The researchers utilized a whole-genome siRNA-based reverse genetic screen to search for defects in the biogenesis and/or maintenance of primary cilia. From their screen, the team was able to identify 112 candidate genes that were either involved in the creation of the organelles or contained mutations that adversely affected cilia development or function.

Interestingly, the results from the collaborative effort found 44 genes involved in the ubiquitin–proteasome pathway, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors that have been shown to be mutated in autosomal dominant form of retinitis pigmentosa, a disorder where primary cilia are thought to play a significant role.

Additionally, the scientists were able to combine the findings from their RNAi screen with previously published exome sequencing data and identify a set of recessive mutations as the causes for the ciliopathies known as Joubert (neurologic disorder) and Jeune (skeletal disorder) syndromes.

“We confirmed that each of the genes on the list were important for cilia using an independent method,” stated co-senior author Ronald Roepman, Ph.D., group leader at the Radboud University Medical Center, Nijmegen. “We then focused in on some of the biochemical processes that are required for a functioning cilium. But the broader picture still has a wealth of similar opportunities for others in the research community.”

The researchers continuing to sift through the genetic data with the hope that therapeutic interventions can be uncovered to help control or cure some of these genetic disorders. The authors concluded with the observation that “our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.”

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