Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

• Published in: Current biology Vol. 29; no. 2; pp. 229 - 241.e6
• Main Authors: Olstad, Emilie W., Ringers, Christa, Hansen, Jan N., Wens, Adinda, Brandt, Cecilia, Wachten, Dagmar, Yaksi, Emre, Jurisch-Yaksi, Nathalie
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21-01-2019; Cell Press
• Subjects: Animals; brain; Brain - physiology; brain ventricle; Cerebral Ventricles - growth & development; cerebrospinal fluid; Cerebrospinal Fluid - physiology; cilia; Cilia - metabolism; ependymal cells; flow; fluid dynamics; foxj1; heartbeat; zebrafish; Zebrafish - growth & development; Zebrafish - physiology; ependymal cells; heartbeat; brain ventricle; foxj1; cerebrospinal fluid; cilia; zebrafish; brain; fluid dynamics; flow
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2018.11.059

Motile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.
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•Spatially organized motile cilia with rotational beats create directional CSF flow•Ciliary beating, heartbeat, and locomotion generate distinct components of CSF flow•Joint action of these components balances CSF compartmentalization and dispersion•Disruption of ciliary beating leads to ventricular defects during brain development
Olstad et al. show that the cerebrospinal fluid flow dynamics in vivo are controlled by ciliary beating, heartbeat pulsations, and bodily movements. Together, these components balance the compartmentalization and the dispersion of CSF across the brain ventricles. Genetic disruption of ciliary beating leads to ventricular defects during development.