The evolutionarily conserved choroid plexus maintains the homeostasis of brain ventricles in zebrafish

The choroid plexus produces cerebrospinal fluid (CSF) by transporting ions and water from adjacent blood vessels to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules and serving as a CSF-blood barrier and immune interface. Previous studies highlighted that several transporters on the epithelial cells transport water and ions into the ventricles and tight junctions of the cells are involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and influence brain physiology remain elusive. To gain novel insights into the physiological roles of the choroid plexus, we use zebrafish as a model system, benefiting from its dorsal and optically accessible position. Upon histological and transcriptomic analyses, we revealed that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and it expresses all transporters necessary for CSF production. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line enabling to ablate specifically the choroid plexus epithelial cells. Using the ablation system, we discovered a reduction of the brain ventricular sizes without alterations of the CSF-blood barrier in the choroid plexus ablated fish. Altogether, our findings demonstrated that the evolutionarily conserved zebrafish choroid plexus is critical for sustaining the homeostasis of the brain ventricles. Based on these findings, our long-term goal is aiming to unravel how the choroid plexus epithelial cells regulate brain physiology and behaviors in health and diseases.