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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kadur Lakshminarasimha Murthy, P; Srinivasan, T; Bochter, MS; Xi, R; Varanko, AK; Tung, K-L; Semerci, F; Xu, K; Maletic-Savatic, M; Cole, SE; Shen, X

Published Date

  • April 9, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 29629872

Pubmed Central ID

  • 29629872

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.35710

Language

  • eng