Abstract
BackgroundThe choroid plexus (CP) is an epithelial and vascular structure in the ventricular system of the brain that is a critical part of the blood-brain barrier. The CP has two primary functions, 1) to produce and regulate components of the cerebral spinal fluid, and 2) to inhibit entry into the brain of exogenous substances. Despite its importance in neurobiology, little is known about how this structure forms.Methodology and Principal FindingsHere we show that the transposon-mediated enhancer trap zebrafish line EtMn16 expresses green fluorescent protein within a population of cells that migrate toward the midline and coalesce to form the definitive CP. We further demonstrate the development of the integral vascular network of the definitive CP. Utilizing pharmacologic pan-notch inhibition and specific morpholino-mediated knockdown, we demonstrate a requirement for Notch signaling in choroid plexus development. We identify three Notch signaling pathway members as mediating this effect, notch1b, deltaA, and deltaD.Conclusions and SignificanceThis work is the first to identify the zebrafish choroid plexus and to characterize its epithelial and vasculature integration. This study, in the context of other comparative anatomical studies, strongly indicates a conserved mechanism for development of the CP. Finally, we characterize a requirement for Notch signaling in the developing CP. This establishes the zebrafish CP as an important new system for the determination of key signaling pathways in the formation of this essential component of the vertebrate brain.
Highlights
The choroid plexus (CP) is a set of vital structures in the brain central to the formation, regulation and protection of the cerebral spinal fluid (CSF)
This study provides the first description of CP development in vivo and demonstrates a role for Notch signaling in myelencephalic choroid plexus (mCP) development
Identification of the zebrafish CP EtMn16 is a GFP expressing transposon-mediated enhancer trap line identified as part of an ongoing genomic annotation project [6]
Summary
The choroid plexus (CP) is a set of vital structures in the brain central to the formation, regulation and protection of the cerebral spinal fluid (CSF). The polarized epithelial cells surround the stroma and vascular core and exist as a monolayer, with their basal surface facing the stroma, and their apical surface extending microvilli and cilia into the CSF-filled ventricles [3]. Classic studies in human embryology place the onset of CP development at 6 weeks gestation and continuing past birth [1]. The first of the choroid plexuses to develop is the fourth ventricle CP (4vCP), or its orthologue the myelencephalic choroid plexus (mCP), in other organisms including telosts [1,5]. Despite its importance in neurobiology, little is known about how this structure forms
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