Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate


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. © 2022. The Author(s).

Authors Parichha A, Suresh V, Chatterjee M, Kshirsagar A, Ben-Reuven L, Olender T, Taketo MM, Radosevic V, Bobic-Rasonja M, Trnski S, Holtzman MJ, Jovanov-Milosevic N, Reiner O, Tole S
Journal Nature communications
Publication Date 2022 Feb 2;13(1):633
PubMed 35110543
PubMed Central PMC8810795
DOI 10.1038/s41467-021-27602-z

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