Format

Send to

Choose Destination
Elife. 2018 Apr 9;7. pii: e35710. doi: 10.7554/eLife.35710.

Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis.

Author information

1
Center for Genomics and Computational Biology, Department of Biomedical Engineering, Duke University, Durham, United States.
2
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, United States.
3
Mienig School of Biomedical Engineering, Cornell University, Ithaca, United States.
4
Department of Molecular Genetics, Ohio State University, Columbus, United States.
5
Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States.
6
Department of Pediatrics, Baylor College of Medicine, Houston, United States.
7
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, United States.
8
School of Electrical and Computer Engineering, Cornell University, Ithaca, United States.
#
Contributed equally

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.

KEYWORDS:

Fringe; Glycosylation; Intestinal Crypts; Lgr5+ Stem Cell; Notch Signalling; cell biology; developmental biology; mouse; stem cells

PMID:
29629872
PMCID:
PMC5896954
DOI:
10.7554/eLife.35710
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

PK, TS, MB, RX, AV, KT, FS, KX, MM, SC, XS No competing interests declared

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center