Development and Notch signaling requirements of the zebrafish choroid plexus.
BACKGROUND
The 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.


RESULTS
Here we show that the transposon-mediated enhancer trap zebrafish line Et(Mn16) 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
This 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.
Bill
Brent R
BR
Department of Genetics, Cell and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
Balciunas
Darius
D
McCarra
Joshua A
JA
Young
Eric D
ED
Xiong
Toua
T
Spahn
Ashley M
AM
Garcia-Lecea
Marta
M
Korzh
Vladimir
V
Ekker
Stephen C
SC
Schimmenti
Lisa A
LA