Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

The choroid plexus (CP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the CP epithelium (CPe) arises from the Wnt- and Bmp- expressing cortical hem. We examined the role of canonical Wnt signaling in CPe development and report that the mouse and human embryonic CPe expresses molecules in this pathway. Either loss of function or constitutive activation of β-catenin, a key mediator of canonical Wnt signaling, causes a profound disruption of mouse CPe development. Loss of β-catenin results in a dysmorphic CPe, while constitutive activation of β-catenin causes a loss of CPe identity and a transformation of this tissue to a hippocampal-like identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. Our results indicate that canonical Wnt signaling is required in a precisely regulated manner for normal CP development in the mammalian brain.