Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
24 11 2023
24 11 2023
Historique:
medline:
27
11
2023
pubmed:
24
11
2023
entrez:
24
11
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38000028
doi: 10.1126/sciadv.adh9673
pmc: PMC10672176
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadh9673Subventions
Organisme : Czech Science Foundation
ID : GX19-28347X
Organisme : National Institute for Cancer Research
ID : LX22NPO5102
Organisme : Dutch Cancer Society
ID : 13112
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