Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2-Reference-Cited by-同舟云学术

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

Published:2023-11-24 Issue:47 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Colozza Gabriele¹^ORCID,Lee Heetak¹²^ORCID,Merenda Alessandra³^ORCID,Wu Szu-Hsien Sam¹,Català-Bordes Andrea¹^ORCID,Radaszkiewicz Tomasz W.⁴^ORCID,Jordens Ingrid⁵^ORCID,Lee Ji-Hyun¹²^ORCID,Bamford Aileen-Diane¹⁶,Farnhammer Fiona¹⁷^ORCID,Low Teck Yew⁸^ORCID,Maurice Madelon M.⁵^ORCID,Bryja Vítězslav⁴⁹^ORCID,Kim Jihoon¹¹⁰^ORCID,Koo Bon-Kyoung¹²¹¹^ORCID

Affiliation:

1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.

2. Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseong-gu, Daejeon 34126, Republic of Korea.

3. HUB Organoids, Utrecht, Netherlands.

4. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

5. Oncode Institute and Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands.

6. Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.

7. Division of Metabolism and Division of Oncology, University Children’s Hospital Zurich and Children’s Research Center, University of Zurich, 8032 Zurich, Switzerland.

8. UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia (UKM), Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.

9. Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.

10. Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.

11. Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adh9673

Reference62 articles.

1. Cell fate specification and differentiation in the adult mammalian intestine

2. Clone wars: From molecules to cell competition in intestinal stem cell homeostasis and disease

3. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities

4. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

5. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner