Wnt信号通路
干瘪的
细胞生物学
衣冠不整
LRP5
生物
LRP6型
WNT3A型
潘尼斯电池
信号转导
生物化学
小肠
作者
Gabriele Colozza,Heetak Lee,Alessandra Merenda,Wu Ss,Andrea Català-Bordes,Tomasz Radaszkiewicz,Ingrid Jordens,Ji-Hyun Lee,Aileen-Diane Bamford,Fiona Farnhammer,Teck Yew Low,Madelon M. Maurice,Vı́tězslav Bryja,J. Kim,Bon‐Kyoung Koo
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-11-24
卷期号:9 (47)
被引量:3
标识
DOI:10.1126/sciadv.adh9673
摘要
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.
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