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Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2
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SYSNO ASEP 0583497 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2 Author(s) Colozza, G. (AT)
Lee, H. (AT)
Merenda, A. (NL)
Wu, S. S. (AT)
Catala-Bordes, A. (AT)
Radaszkiewicz, T.W. (CZ)
Jordens, I. (NL)
Lee, J. H. (JP)
Bamford, A. (AT)
Farnhammer, F. (AT)
Low, T. Y. (MY)
Maurice, M. M. (NL)
Bryja, Vítězslav (BFU-R) RID, ORCID
Kim, J. (AT)
Koo, B. (AT)Number of authors 15 Article number eadh9673 Source Title Science Advances. - : American Association for the Advancement of Science - ISSN 2375-2548
Roč. 9, č. 47 (2023)Number of pages 18 s. Language eng - English Country US - United States Keywords convergent extension ; wnt/beta-catenin ; endocytosis ; receptors ; proteins ; activation ; growth ; lgr5 ; rho Subject RIV CE - Biochemistry OECD category Biochemical research methods Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 001139850400006 DOI 10.1126/sciadv.adh9673 Annotation The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate beta-catenin-dependent (canonical) orindependent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2024 Electronic address https://www.science.org/doi/10.1126/sciadv.adh9673
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