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Authors & Affiliations
Kim Hoa Ho, Adrien Candat, Valentina Scarpetta, Marion Faucourt, Solene Weill, Chiara Salio, Elisa D’Este, Martin Meschkat, Christian A. Wurm, Matthias Kneussel, Carsten Janke, Maria M. Magiera, Auguste Genovesio, Alice Meunier, Marco Sassoè-Pognetto, Monika S. Brill, Nathalie Spassky, Annarita Patrizi
Abstract
Choroid plexus (ChP) is located in cerebral ventricles, where it produces cerebrospinal fluid (CSF), forms the selective blood-CSF barrier and controls the homeostasis of the central nervous system. ChP is primarily composed of a monolayer of specialized epithelial cells producing cerebrospinal fluid. Differentiated ChP epithelial cells harbor multiple cilia on the CSF-facing surface, but their development and function are still controversial. We have delineated the sequential progression of cilia formation in the ChP epithelial cells by exploiting super-resolution microscopy techniques and mouse genetics. Our findings indicate that choroidal cilia formation follows an unconventional, orchestrated series of spatiotemporally regulated events. We show that multiciliogenesis in the ChP starts with embryonic centriole amplification and culminates in the formation of nodal-like 9+0 cilia, which exhibit both primary and motile characteristics. During early postnatal stages, ChP cilia experience axoneme resorption, leaving ChP epithelial cells with basal bodies either devoid of cilia, or associated with extremely short ones. The same phenotype was observed also in humans, suggesting ciliary resorption is preserved among species. Notably, we discovered that axoneme resorption is orchestrated by the microtubule-severing enzyme spastin, and possibly regulated by the reduction of microtubule polyE. In conclusion, ChP cilia represent an important differentiation marker of ChP epithelium, and their unconventional developmental stages call for more investigations on their functional role and how it may change through lifetime.