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bioRxiv · 10.1101/2020.12.08.415588

Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

Parichha, A.·Suresh, V.·Chatterjee, M.·Khsirsagar, A.·Ben-Reuven, L.·Olender, T.·Taketo, M. M.·Radosevic, V.·Bobic-Rasonja, M.·Trinski, S.·Jovanov Milosevic, N.·Reiner, O.·Tole, S.
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Abstract

The choroid plexus (ChP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the ChP epithelium (ChPe) arises from the Wnt-expressing cortical hem. Embryonic mouse and human ChPe both express nuclear {beta}-CATENIN, a canonical Wnt signaling pathway effector, indicating that this pathway is active during ChPe development. Point mutations in human {beta}-CATENIN result in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of ChPe identity and an apparent transformation of the ChPe to a neuronal identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. The ChPe is also disrupted when {beta}-Catenin is conditionally inactivated in the mouse. Together, our results indicate that canonical Wnt signaling is required in a precise and regulated manner for normal ChPe development in the mammalian brain.

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Parichha, A., Suresh, V., Chatterjee, M., Khsirsagar, A., Ben-Reuven, L., Olender, T., Taketo, M. M., Radosevic, V., Bobic-Rasonja, M., Trinski, S., Jovanov Milosevic, N., Reiner, O., Tole, S.. 2020-12-09. Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development. https://doi.org/10.1101/2020.12.08.415588

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