Ependymal cells in adulthood

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Ependymal cells are one of 4 glia cell types in the central nervous system (CNS). They are epithelial brain barrier cells that are maintained throughout life, and line the entire brain ventricular system and spinal canal. They are the major cerebral spinal fluid (CSF) facing cell of the CNS with the capacity to sense CSF dynamics and regulate its distribution. There are 3 major known subtypes that are predicted to have diverse functions based on their morphological features, yet it remains to be determined how these cells are maintained; the extent of functions they have, as well as the diverse mechanisms underlying how they regulate brain function. As an early career investigator, my lab is developing a long-term program centred around understanding ependymal cell biology including the development of advanced techniques for studying ependymal cells using in vivo, ex vivo and in vitro assays. In the current proposal, my short-term objectives focus on interrogating mouse ependymal cells in vivo to assess the mechanisms of maintenance using a transgenic fate mapping strategy; characterize their diversity using advanced bioinformatics; as well as interrogate a defined role for these cells in maintaining brain function using an inducible ependymal cell KO system. AIM 1: Assess how ependymal cells are maintained in adulthood Most glia cells are replaced by precursor cells throughout life, but at very slow rates in normal circumstances. To establish whether this occurs in the context of ependymal cell maintenance, we will use a mouse fate mapping model to permanently label ependymal cells to track whether these cells are maintained long-term, increase in number, or are lost. This will provide insights into how ependymal cells are maintained. AIM 2: Characterize the heterogeneity of ependymal cells in adulthood Little is known about the transcriptional profile that drives divergent ependymal cell roles. To address this question, we will perform advanced bioinformatic analysis assessing single cell datasets composed of ependymal cells, and validate findings using tissue sections for in situ hybridization. This will provide insights into the degree of ependymal cell heterogeneity as well as provide unbiased suggestions as to repertoire of functions that these cells have. AIM 3: Assess the function of ependymal cell in adulthood Ependymal cells are equipped with motile cilia, and the beating of these cilia generates directional fluid movement, yet the importance of ependymal cell-mediated CSF movement in adulthood has not been assessed. We will interrogate this following the KO of a cilia gene, CDCC39, only in ependymal cells in floxed mice. Studying this will provide critical insights into how ependymal cells regulate CSF movement and whether this is important for maintaining brain homeostasis. Our outcomes will advance our understanding of adult ependymal cell biology, and their importance for maintaining brain function.