BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors

• DOI: 10.1523/jneurosci.3227-12.2012
• Publication Date: 2012-11-07T17:38:02Z
• Authors: Momoko Watanabe; Young-Jin Kang; Lauren M. Davies; Sanket Meghpara; Kimbley Lau; Chi-Yeh Chung; Jaymin Kathiriya; Anna-Katerina Had...; Edwin S. Monuki
• Keywords: Neuroepithelial cell; Cell fate determination; Choroid

Choroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the CSF blood–CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease, transplant studies provided proof-of-concept for CPEC-based therapies. However, therapies hindered by inability expand or generate CPECs culture. During development, differentiate from preneurogenic neuroepithelial require bone morphogenetic protein (BMP) signaling, but whether BMPs suffice induction is unknown. Here we provide evidence BMP4 sufficiency induce fate neural progenitors derived mouse embryonic stem (ESCs). specification was restricted an early time period after culture, with peak competency correlating rather than radial glia. In addition molecular, cellular, ultrastructural criteria, (dCPECs) had functions that were indistinguishable primary CPECs, including self-assembly into secretory vesicles integration endogenous choroid epithelium following intraventricular injection. We then used dCPECs human ESC-derived cells. These findings demonstrate instruct fate, repertoire of cell-derived derivatives herald dCPEC-based therapeutic applications aimed at unique interface between blood, CSF, brain governed CPECs.