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

Publication ,  Journal Article
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 in: Elife
April 9, 2018

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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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

April 9, 2018

Volume

7

Location

England

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Receptors, Notch
  • Receptors, G-Protein-Coupled
  • Proteins
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins
 

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Kadur Lakshminarasimha Murthy, P., Srinivasan, T., Bochter, M. S., Xi, R., Varanko, A. K., Tung, K.-L., … Shen, X. (2018). Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis. Elife, 7. https://doi.org/10.7554/eLife.35710
Kadur Lakshminarasimha Murthy, Preetish, Tara Srinivasan, Matthew S. Bochter, Rui Xi, Anastasia Kristine Varanko, Kuei-Ling Tung, Fatih Semerci, et al. “Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis.Elife 7 (April 9, 2018). https://doi.org/10.7554/eLife.35710.
Kadur Lakshminarasimha Murthy P, Srinivasan T, Bochter MS, Xi R, Varanko AK, Tung K-L, et al. Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis. Elife. 2018 Apr 9;7.
Kadur Lakshminarasimha Murthy, Preetish, et al. “Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis.Elife, vol. 7, Apr. 2018. Pubmed, doi:10.7554/eLife.35710.
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. Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis. Elife. 2018 Apr 9;7.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

April 9, 2018

Volume

7

Location

England

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Receptors, Notch
  • Receptors, G-Protein-Coupled
  • Proteins
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins