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Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

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Title
Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2
Author(s)
Colozza, Gabriele; Heetak Lee; Merenda, Alessandra; Wu, Szu-Hsien Sam; Català-Bordes, Andrea; Radaszkiewicz, Tomasz W.; Jordens, Ingrid; Ji-Hyun Lee; Bamford, Aileen-Diane; Farnhammer, Fiona; Low, Teck Yew; Maurice, Madelon M.; Bryja, Vítězslav; Kim, Jihoon; Bon-Kyoung Koo
Publication Date
2023-11
Journal
Science advances, v.9, no.47
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
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 β-catenin-dependent (canonical) or -independent (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.
URI
https://pr.ibs.re.kr/handle/8788114/14721
DOI
10.1126/sciadv.adh9673
ISSN
2375-2548
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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