J 2023

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

COLOZZA, Gabriele; Heetak LEE; Alessandra MERENDA; Sam Wu SZU-HSIEN; Andrea CATALÀ-BORDES et al.

Basic information

Original name

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

Authors

COLOZZA, Gabriele; Heetak LEE; Alessandra MERENDA; Sam Wu SZU-HSIEN; Andrea CATALÀ-BORDES; Tomasz Witold RADASZKIEWICZ; Ingrid JORDENS; Lee JI-HYUN; Bamford AILEEN-DIANE; Fiona FARNHAMMER; Teck Yew LOW; Madelon M MAURICE; Vítězslav BRYJA; Jihoon KIM and Koo BON-KYOUNG

Edition

Science Advances, Washington, DC, American association for the advancement of science, 2023, 2375-2548

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

Marked to be transferred to RIV

Yes

RIV identification code

RIV/00216224:14310/23:00132483

Organization

Přírodovědecká fakulta – Repository – Repository

EID Scopus

Keywords in English

CONVERGENT EXTENSION; WNT/BETA-CATENIN; ENDOCYTOSIS; RECEPTORS; PROTEINS; ACTIVATION; GROWTH; LGR5; RHO

Links

GX19-28347X, research and development project. LM2023050, research and development project. LX22NPO5102, research and development project.
Changed: 26/4/2024 04:07, RNDr. Daniel Jakubík

Abstract

In the original language

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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