TY - JOUR
T1 - Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate
AU - Parichha, Arpan
AU - Suresh, Varun
AU - Chatterjee, Mallika
AU - Kshirsagar, Aditya
AU - Ben-Reuven, Lihi
AU - Olender, Tsviya
AU - Taketo, M. Mark
AU - Radosevic, Velena
AU - Bobic-Rasonja, Mihaela
AU - Trnski, Sara
AU - Holtzman, Michael J.
AU - Jovanov-Milosevic, Nataša
AU - Reiner, Orly
AU - Tole, Shubha
N1 - Funding Information:
We thank K. Millen (Seattle Children’s hospital) for the kind gift of the Lmx1aCre mouse line; Shital Suryavanshi and the animal house staff of the Tata Institute for Fundamental Research (TIFR) for excellent support. This work was supported by a Wellcome Trust-Department of Biotechnology India Alliance Early Career Fellowship (IA-E-12-1-500765, MC); by the Canada-Israel Health Research Initiative, jointly funded by the Canadian Institutes of Health Research, the Israel Science Foundation, the International Development Research Centre, Canada and the Azrieli Foundation (ST, grant # 108875); intramural funds from TIFR-DAE (12-R&D-TFR-5.10-0100RTI2001). Research in the Reiner lab is supported by ISF-National Science Foundation of China (NSFC) joint research program (Grant No. 2449/16), with the aid of a grant no. 2397/18 from the Canadian Institutes of Health Research (CIHR), the International Development Research Center (IDRC), the ISF, a grant from the Ministry of Science & Technology, Israel & The Ministry of Science and Technology of the People’s Republic of China, German-Israeli Foundation (GIF; Grant no. I-1476-203.13/2018), and United States-Israel Binational Science Foundation (BSF; Grant No. 2017006). In addition, by the Helen and Martin Kimmel Institute for Stem Cell Research, Nella and Leon Benoziyo Center for Neurological Diseases, David and Fela Shapell Family Center for Genetic Disorders Research, Brenden-Mann Women’s Innovation Impact Fund, Richard F. Goodman Yale/Weizmann Exchange Program, The Irving B. Harris Fund for New Directions in Brain Research, Irving Bieber, MD, and Toby Bieber, MD. Memorial Research Fund, Leff Family, Barbara & Roberto Kaminitz, Sergio & Sônia Lozinsky, Debbie Koren. Jack and Lenore Lowenthal, Dears Foundation. The study on the human brains was financed by Croatian Science Foundation projects IP-2019-04-3182; DOK-2018-01-3771; DOK-2015-10-3939 to NJM and the Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience (GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund). The collaboration was initiated throughout COST Action 16118. We thank the members of Tole lab, Reiner lab, and Jovanov lab for their valuable inputs and discussion.
Funding Information:
We thank K. Millen (Seattle Children?s hospital) for the kind gift of the Lmx1aCre mouse line; Shital Suryavanshi and the animal house staff of the Tata Institute for Fundamental Research (TIFR) for excellent support. This work was supported by a Wellcome Trust-Department of Biotechnology India Alliance Early Career Fellowship (IA-E-12-1-500765, MC); by the Canada-Israel Health Research Initiative, jointly funded by the Canadian Institutes of Health Research, the Israel Science Foundation, the International Development Research Centre, Canada and the Azrieli Foundation (ST, grant # 108875); intramural funds from TIFR-DAE (12-R&D-TFR-5.10-0100RTI2001). Research in the Reiner lab is supported by ISF-National Science Foundation of China (NSFC) joint research program (Grant No. 2449/16), with the aid of a grant no. 2397/18 from the Canadian Institutes of Health Research (CIHR), the International Development Research Center (IDRC), the ISF, a grant from the Ministry of Science & Technology, Israel & The Ministry of Science and Technology of the People?s Republic of China, German-Israeli Foundation (GIF; Grant no. I-1476-203.13/2018), and United States-Israel Binational Science Foundation (BSF; Grant No. 2017006). In addition, by the Helen and Martin Kimmel Institute for Stem Cell Research, Nella and Leon Benoziyo Center for Neurological Diseases, David and Fela Shapell Family Center for Genetic Disorders Research, Brenden-Mann Women?s Innovation Impact Fund, Richard F. Goodman Yale/Weizmann Exchange Program, The Irving B. Harris Fund for New Directions in Brain Research, Irving Bieber, MD, and Toby Bieber, MD. Memorial Research Fund, Leff Family, Barbara & Roberto Kaminitz, Sergio & S?nia Lozinsky, Debbie Koren. Jack and Lenore Lowenthal, Dears Foundation. The study on the human brains was financed by Croatian Science Foundation projects IP-2019-04-3182; DOK-2018-01-3771; DOK-2015-10-3939 to NJM and the Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience (GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund). The collaboration was initiated throughout COST Action 16118. We thank the members of Tole lab, Reiner lab, and Jovanov lab for their valuable inputs and discussion.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124058684&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-27602-z
DO - 10.1038/s41467-021-27602-z
M3 - Article
C2 - 35110543
AN - SCOPUS:85124058684
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 633
ER -