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bioRxiv · 10.1101/376152

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

Barr, M. M.·De Vore, D. M.·Knobel, K. M.·Nguyen, K. C. Q.·Hall, D. H.
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Abstract

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.

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Barr, M. M., De Vore, D. M., Knobel, K. M., Nguyen, K. C. Q., Hall, D. H.. 2018-07-24. Extracellular matrix regulates morphogenesis and function of ciliated sensory organs in Caenorhabditis elegans. https://doi.org/10.1101/376152

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