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, Shubha Tole

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Article number633
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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