Researchers at the University College Dublin (UCD) Conway Institute of Biomolecular and Biomedical Research in Ireland have discovered new information on a gene that is involved in the development of Joubert syndrome, a genetic disorder that affects the brain stem. The team hopes that the results, which are published in the Journal of Cell Biology, will lead to a greater understanding of a range of cerebellar disorders. Joubert syndrome is a rare genetic disease that affects the cerebellar vermis, the part of the brain that controls muscle coordination, balance and movement. In Joubert syndrome, the cerebellum and brain stem do not develop properly, resulting in poor muscle control. Other symptoms include liver and kidney problems, blindness, mild to moderate degrees of mental handicap and bone abnormalities such as cleft lip or palate, or extra fingers and toes. One of the genes associated with JSRDs (Joubert syndrome and related disorders) is Arl13b, which codes for a protein that scientists know plays a role in the formation and possibly the function of cilia, the tiny hair-like sensory organelles that protrude from the surface of cells. To try to discover the relationship between Arl13b and cilia the UCD team collaborated with scientists at the University of Tokyo, Japan to carry out experiments with cilia in a species of tiny worm called Caenorhabditis elegans. The research revealed that the Arl13b proteins use lipid anchors to associate with the ciliary membrane. They also showed that as well as causing the ciliary membrane to become misshapen, disrupting the function of the Arl13b protein in the worms can affect the ability of other proteins to distribute properly within the ciliary membrane. The tests established that the Arl13b protein is needed for the normal functioning of a protein transport system in cilia. The research team has now proposed a new working model for Arl13b, where it is responsible for regulating important ciliary membrane properties such as shape and transmembrane protein distributions. Cilia are present on nearly all cells of the human body, yet until 20 years ago many scientists believed that they were redundant structures that did not really serve a function. They are now realising that cilia play an important role in movement and sensory functions including signalling pathways. Defects in ciliary structure are increasingly being associated with many diseases and syndromes (called ciliopathies). These include polycystic kidneys and livers, degeneration of the retina, bone abnormalities, hydrocephalus, mental retardation, obesity, diabetes and cancer. Commenting on the research results, Dr Oliver Blacque, from UCD's Conway Institute of Biomolecular and Biomedical Research, said: 'That Arl13b associates with ciliary membranes and is required for cilium structure/function in both worms and mammals demonstrates the remarkable evolutionary conservation of how this small G-protein functions. 'For patients with Joubert syndrome, these findings provide a greater understanding of the pathomechanisms of the disease and refine our working hypothesises, thereby instructing future research into JSRDs and possibly other ciliopathies.'