Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Arpan Parichha, Varun Suresh, Mallika Chatterjee, Aditya Kshirsagar, Lihi Ben-Reuven, Tsviya Olender, M. Mark Taketo, Velena Radosevic, Mihaela Bobic-Rasonja, Sara Trnski, Michael J. Holtzman, Nataša Jovanov-Milosevic (), Orly Reiner () and Shubha Tole ()
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Arpan Parichha: Tata Institute of Fundamental Research
Varun Suresh: Tata Institute of Fundamental Research
Mallika Chatterjee: Tata Institute of Fundamental Research
Aditya Kshirsagar: Weizmann Institute of Science
Lihi Ben-Reuven: Weizmann Institute of Science
Tsviya Olender: Weizmann Institute of Science
M. Mark Taketo: Kyoto University (Yoshida-Konoé-Cho, Sakyo)
Velena Radosevic: School of Medicine University of Zagreb
Mihaela Bobic-Rasonja: School of Medicine University of Zagreb
Sara Trnski: School of Medicine University of Zagreb
Michael J. Holtzman: Washington University
Nataša Jovanov-Milosevic: School of Medicine University of Zagreb
Orly Reiner: Weizmann Institute of Science
Shubha Tole: Tata Institute of Fundamental Research

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27602-z

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