A distinct population of ependymal cells (E2) in the forebrain of mice and humans are described, identified as a novel CSF-sensing ependymal cell type and provide a cellular target for the CSF signaling.
Abstract
Ependymal (E1) cells, with their tufts of ∼50 motile cilia, line the walls of the brain ventricles and help propel the cerebrospinal fluid (CSF). The CSF is rich in signaling molecules, but the cellular targets that detect these signals and their function remain unknown. Here, we describe a distinct population of ependymal cells (E2) in the forebrain of mice and humans, the majority having only 1 or 2 cilia. These cilia were motile, but unlike E1 cells’ cilia, their pattern of motility and high expression of Arl13b and Inpp5e suggest a sensory function. E2 cells were characterized by an enormous, donut-like basal body that contained an increased number and size of subdistal appendages. In mice, E2 cells were mostly born in the embryo, but completed their differentiation in juveniles and young adults; they were found at higher densities in regions of high CSF flow and neurogenesis. E2 cilia contained the G protein-coupled receptor Smoothened, which accumulated in their cilia upon exposure to Sonic Hedgehog (Shh). Together, these findings identify E2 cells as a novel CSF-sensing ependymal cell type and provide a cellular target for the CSF signaling.
The structural and functional organization of the ependymal cilia is described and how ciliary defects range from severe developmental disruptions causing neonatal hydrocephalus to subtle maintenance defects underlying late-onset forms of the disease are discussed.
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