이희탁 (Vienna BioCenter, IBS) | 한빛사논문 > 한빛사

한빛사논문

조회672

이희탁Heetak Lee

Vienna BioCenter, IBS

Sci. Adv., Nov 24 2023, 9 (47) | https://doi.org/10.1126/sciadv.adh9673 Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

Gabriele Colozza ^{1 †}, Heetak Lee ^{1 2 †}, Alessandra Merenda ^{3 †}, Szu-Hsien Sam Wu ¹, Andrea Català-Bordes ¹, Tomasz W Radaszkiewicz ⁴, Ingrid Jordens ⁵, Ji-Hyun Lee ^{1 2}, Aileen-Diane Bamford^{1 6}, Fiona Farnhammer ^{1 7}, Teck Yew Low ⁸, Madelon M Maurice ⁵, Vítězslav Bryja^{4 9}, Jihoon Kim ^{1 10 *}, Bon-Kyoung Koo ^{1 2 11 *}

¹Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.
²Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseong-gu, Daejeon 34126, Republic of Korea.
³HUB Organoids, Utrecht, Netherlands.
⁴Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
⁵Oncode Institute and Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands.
⁶Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
⁷Division of Metabolism and Division of Oncology, University Children's Hospital Zurich and Children's Research Center, University of Zurich, 8032 Zurich, Switzerland.
⁸UKM Medical Molecular Biology Institute (UMBI), University Kebangsaan Malaysia (UKM), Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.
⁹Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
¹⁰Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.
¹¹Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

^†These authors contributed equally to this work
^*Corresponding authors: correspondence to Jihoon Kim or Bon-Kyoung Koo

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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-28)
연구진국내(교신)+국외 연구진
분야 생명과학 > 노화/암생물학

댓글 작성 로그인

CV 열람하기

연락처 보기