Abstract
The choroid plexus secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the choroid plexus epithelium arises from the Wnt- expressing cortical hem. Canonical Wnt signaling pathway molecules such as nuclear β-CATENIN are expressed in the mouse and human embryonic choroid plexus epithelium indicating that this pathway is active. Point mutations in human β-CATENIN are known to result in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of choroid plexus epithelial identity and an apparent transformation of this tissue to a neuronal identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell derived organoids. The choroid plexus is also disrupted when β-Catenin is conditionally inactivated. Together, our results indicate that canonical Wnt signaling is required in a precise and regulated manner for normal choroid plexus development in the mammalian brain.
Highlights
The choroid plexus secretes cerebrospinal fluid and is critical for the development and function of the brain
Our results indicate that controlled levels of canonical Wnt signaling is critical for ChP epithelium (ChPe) specification and morphogenesis and that this mechanism appears to be conserved in humans and rodents
We examined whether the molecular machinery required for processing canonical Wnt signaling is present in the developing ChPe at the relevant stages in both human and mouse embryos
Summary
The choroid plexus secretes cerebrospinal fluid and is critical for the development and function of the brain. Canonical Wnt signaling pathway molecules such as nuclear β-CATENIN are expressed in the mouse and human embryonic choroid plexus epithelium indicating that this pathway is active. A role for canonical Wnt signaling in ChPe development is suggested by the observation that the choroid plexus appears to be reduced in the Wnt3a null mutant[19]. Exon 3 of the β-CATENIN gene is a hotspot for several mutations, including point mutations and deletions associated with various forms of cancer[21] The effects of these mutations on ChP-related disorders have not been studied, even though ChP papillomas have been reported to display upregulation of canonical Wnt signaling[22].
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