TY - JOUR
T1 - Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2
AU - Colozza, Gabriele
AU - Lee, Heetak
AU - Merenda, Alessandra
AU - Wu, Szu Hsien Sam
AU - Català-Bordes, Andrea
AU - Radaszkiewicz, Tomasz W.
AU - Jordens, Ingrid
AU - Lee, Ji Hyun
AU - Bamford, Aileen Diane
AU - Farnhammer, Fiona
AU - Low, Teck Yew
AU - Maurice, Madelon M.
AU - Bryja, Vítězslav
AU - Kim, Jihoon
AU - Koo, Bon Kyoung
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2023/11/24
Y1 - 2023/11/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85177761800&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adh9673
DO - 10.1126/sciadv.adh9673
M3 - Article
C2 - 38000028
AN - SCOPUS:85177761800
VL - 9
JO - Science advances
JF - Science advances
IS - 47
M1 - eadh9673
ER -