Extracellular matrix regulates morphogenesis and function of ciliated sensory organs in Caenorhabditis elegans

摘要: ABSTRACT Cilia and extracellular vesicles (EVs) are signaling organelles that play important roles in human health disease. In C. elegans mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 polycystin-2 localize to both cilia EVs, act same genetic pathway, function a sensory capacity, suggesting ancient conservation. Hence, nematode offers an excellent system which address central questions regarding biology of cilia, polycystins. We discovered unexpected role mec-1, mec-5, mec-9 genes encoding matrix (ECM) components. determined these ECM regulate polycystin localization function, ciliary EV release, length, dendritic morphology, neuron-glia interactions. Abnormal fibrosis observed ciliopathies such as ADPKD, nephronophthisis, Bardet-Biedl Syndrome. Our studies reveal multifaceted for proteins ciliated nervous worm provide powerful new vivo model study relationship between ECM, polycystins, ciliopathies.