bioRxiv Science⌕ Search

Biology subjects

De Vore, D. M.

Publications and source records attributed to De Vore, D. M..

2 recordsLinked to original sources

The extracellular matrix gene mec-9 regulates C. elegans sensory cilia

Cilia are critical sensory organelles that project from the cell surface into the tissue environment, where they are surrounded by extracellular matrix (ECM). Abnormal ECM and fibrosis are two hallmarks of ciliopathies, yet the relationship between cilia and ECM is not well understood. Using the sense organs of C. elegans as a model, we found that a neomorphic mutation in the ECM gene mec-9 impacts sensory cilia function, ciliary protein localization, microtubule ultrastructure, and shedding of ciliary extracellular vesicles (EVs). We show that mec-9 is not expressed in EV releasing neurons, but rather by companion neurons in the sense organs, and may act cell non-autonomously. Our studies reveal pleiotropic roles for mec-9 in the C. elegans ciliated nervous system and provide an in vivo model to study the relationship between cilia and ECM.

cell biology↗

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

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

cell biology↗