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Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.
- Source :
-
Science advances [Sci Adv] 2023 Nov 24; Vol. 9 (47), pp. eadh9673. Date of Electronic Publication: 2023 Nov 24. - Publication Year :
- 2023
-
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.
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 9
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 38000028
- Full Text :
- https://doi.org/10.1126/sciadv.adh9673