Gene associated with a set of poorly understood rare diseases
IRB Barcelona has identified GEMC1 as a master gene for the generation of multiciliated cells—cells with fine filaments that move fluids and substances—which are found exclusively in the brain, respiratory tract, and reproductive system.
Defects in multiciliated cells lead to ciliopathies—rare and complex diseases that are poorly understood and for which not all causative genes have been identified.
The genomic sequencing of hundreds of patients with diverse types of ciliopathies has revealed that “in many cases the gene responsible is not known”, says Travis Stracker, head of the Genomic Instability and Cancer Lab at the IRB Barcelona. “So many people do not have a molecular diagnosis,” stresses the researcher. “Our work seeks to contribute to bridging this knowledge gap”.
A study on mice by Travis Stracker and his team, in collaboration with Vincenzo Costanzo’s laboratory at the FIRC Institute of Molecular Oncology (IFOM) in Milan, in which they reveal a gene candidate for a subtype of human ciliopathy. The gene in question, GEMC1, is indispensable for the generation of multiciliated cells specific to tissues such as the brain, trachea, lungs and oviducts.
The surface of multiciliated cells is covered by hundreds of cilia. These tiny, hairlike structures serve to circulate cerebrospinal fluid, remove mucus from the respiratory tract, and transport ovum through the oviduct, among other functions. Defects in the generation or function of these cells causes a subtype of ciliopathies called Mucociliary Clearance Disorders.
Specifically, GEMC1-deficient mice produced by Stracker reproduce the symptoms of a rare disease called RGMC (Reduced Generation of Multiple Motile Cilia)—a condition that causes hydrocephaly, severe respiratory infections, and infertility. The work, led by IRB Barcelona PhD student Berta Terré and IFOM postdoctoral researcher Gabriele Piergiovanni, reports that GEMC1 regulates the only two genes known to date that underlie this disease, Multicilin and Cyclin O, thus making it a potential candidate gene for RGMC.
In addition, the study has revealed that GEMC1 is one of the most important genes in the gene signalling cascade for the production of multiciliated cells. This means that this gene affects many others that depend on its expression. The gene expression analysis of this first study has revealed at least 10 new candidate genes related to cilia, as well as dozens that were already known or suspected of being involved in the function of cilia. IRB Barcelona
