Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis
Abstract
Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch activity in the two compartments. At the crypt base, RFNG is enriched in the Paneth cells and increases cell surface expression of DLL1 and DLL4. This promotes Notch activity in the neighbouring Lgr5+ stem cells assisting their self-renewal. Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage . Hence, in the intestinal epithelium, Fringes are present in the ligand-presenting ‘sender’ secretory cells and promote Notch activity in the neighbouring ‘receiver’ cells. Fringes thereby provide for targeted modulation of Notch activity and thus the cell fate in the stem cell zone, or the upper crypt and villus.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 09, 2018
- Source ID
- 10.7554/elife.35710
Entities
People
- Anastasia Kristine Varanko
- Fatih Semerci
- Keli Xu
- Kuei-ling Tung
- Matthew S Bochter
- Mirjana Maletic-Savatic
- Preetish Kadur Lakshminarasimha Murthy
- Rui Xi
- Susan E Cole
- Tara Srinivasan
- Xiling Shen
Organizations
- Baylor College of Medicine
- Cornell University
- Defense Advanced Research Projects Agency
- Duke University
- National Institutes of Health
- National Science Foundation
- Ohio State University
- University of Mississippi