The evolutionary conserved choroid plexus sustains the homeostasis of brain ventricles in zebrafish

Abstract

The choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/565468v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1594039org.highwire.dtl.DTLVardef@877b99org.highwire.dtl.DTLVardef@c3834forg.highwire.dtl.DTLVardef@1e1f787_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe zebrafish choroid plexus has similar anatomical features with the mammalian choroid plexus. C_LIO_LIThe expression of choroid plexus transporters involved in CSF secretion is evolutionarily conserved across vertebrates. C_LIO_LIGeneration of a novel choroid plexus specific driver line shows that the choroid plexus epithelial cells secrete proteins into CSF. C_LIO_LIAblation of the choroid plexus decreases the size of the brain ventricles. C_LI