Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Autor: Michael J. Holtzman, Arpan Parichha, Varun Suresh, Makoto Mark Taketo, Sara Trnski, Orly Reiner, Mihaela Bobić-Rasonja, Velena Radosevic, Aditya Kshirsagar, Lihi Ben-Reuven, Mallika Chatterjee, Nataša Jovanov Milošević, Shubha Tole, Tsviya Olender
Rok vydání: 2020
Předmět:
Popis: 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 β-CATENIN, a canonical Wnt signaling pathway effector, indicating that this pathway is active during ChPe development. Point mutations in human β-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 β-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.
Databáze: OpenAIRE