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

Autor: Preetish Kadur Lakshminarasimha Murthy, Tara Srinivasan, Matthew S Bochter, Rui Xi, Anastasia Kristine Varanko, Kuei-Ling Tung, Fatih Semerci, Keli Xu, Mirjana Maletic-Savatic, Susan E Cole, Xiling Shen
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: eLife, Vol 7 (2018)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.35710
Popis: 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.
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