Intrinsic microtubule destabilization of multiciliated choroid plexus epithelial cells during postnatal lifetime
Choroid plexus (ChP) epithelium is composed of specialized multiciliated cells. By using multiple microscopic techniques, biochemical approaches in various mutant mice and longitudinal analysis from mouse embryogenesis to aging, we show that ChP cilia are built on a gradient of events which are spatio-temporally regulated. We uncover that ChP cilia develop prenatally since early tissue morphogenesis, and proceeds as a multi-step process characterized by basal body multiplication and axoneme formation directly at the apical cellular compartment. Our data also show that choroid plexus cilia contain both primary and motile features. Remarkably, we demonstrate that ChP cilia undergo axoneme resorption, starting from early youth, through a tubulin destabilization process, which is primarily controlled by polyglutamylation levels and could be mitigated by the removal of the microtubule-severing enzyme spastin. Notably, we demonstrate that this phenotype is preserved in human samples.