Frizzled 7 modulates goblet and Paneth cell fate, and maintains homeostasis in mouse intestine

Author:

Gu Nai-Xin1,Guo Yu-Ru2ORCID,Lin Sey-En3,Wang Yen-Hsin4,Lin I.-Hsuan5,Chen Yi-Fan1467ORCID,Yen Yun2589ORCID

Affiliation:

1. College of Medical Science and Technology, Taipei Medical University and Academia Sinica 1 The PhD Program for Translational Medicine , , Taipei 11529 , Taiwan

2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University 2 , Taipei 11031 , Taiwan

3. New Taipei Municipal Tucheng Hospital, Chang Gung Memorial Hospital and Chang Gung University 3 Department of Anatomic Pathology , , New Taipei City 236017 , Taiwan

4. Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University 4 , Taipei 11031 , Taiwan

5. TMU Research Center of Cancer Translational Medicine, Taipei Medical University 5 , Taipei 11031 , Taiwan

6. School of Pharmacy, Taipei Medical University 6 Master Program in Clinical Genomics and Proteomics , , Taipei 11031 , Taiwan

7. College of Medical Science and Technology, Taipei Medical University 7 International Ph.D. Program for Translational Science , , Taipei 11031 , Taiwan

8. College of Medical Science and Technology, Taipei Medical University 8 Ph.D. Program for Cancer Molecular Biology and Drug Discovery , , Taipei 11031 , Taiwan

9. Cancer Center, Taipei Municipal WanFang Hospital 9 , Taipei 116081 , Taiwan

Abstract

ABSTRACT Intestinal homeostasis depends on interactions between the intestinal epithelium, the immune system and the microbiota. Because of these complicated connections, there are many problems that need to be solved. Current research has indicated that genes targeted by Wnt signaling are responsible for controlling intestinal stem cell fate and for modulating intestinal homeostasis. Our data show that loss of frizzled 7 (Fzd7), an important element in Wnt signaling, interrupts the differentiation of mouse intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupts epithelial homeostasis, resulting in a decrease in physical protection in the intestine. Several phenotypes in our Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.

Funder

Ministry of Education

Ministry of Health and Welfare

Ministry of Science and Technology

Taipei Medical University

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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