Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis
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 b...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-04-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/35710 |
| _version_ | 1828166007985799168 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Preetish Kadur Lakshminarasimha Murthy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:53:24Z |
| format | Article |
| id | doaj.art-121926b2a45945929e8a365779ac4c78 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:53:24Z |
| publishDate | 2018-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-121926b2a45945929e8a365779ac4c782022-12-22T03:52:51ZengeLife Sciences Publications LtdeLife2050-084X2018-04-01710.7554/eLife.35710Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasisPreetish Kadur Lakshminarasimha Murthy0https://orcid.org/0000-0002-9762-8376Tara Srinivasan1Matthew S Bochter2https://orcid.org/0000-0001-9607-3770Rui Xi3Anastasia Kristine Varanko4Kuei-Ling Tung5Fatih Semerci6https://orcid.org/0000-0002-0512-1827Keli Xu7Mirjana Maletic-Savatic8https://orcid.org/0000-0002-6548-4662Susan E Cole9Xiling Shen10https://orcid.org/0000-0002-4978-3531Center for Genomics and Computational Biology, Department of Biomedical Engineering, Duke University, Durham, United States; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, United StatesMienig School of Biomedical Engineering, Cornell University, Ithaca, United StatesDepartment of Molecular Genetics, Ohio State University, Columbus, United StatesCenter for Genomics and Computational Biology, Department of Biomedical Engineering, Duke University, Durham, United StatesMienig School of Biomedical Engineering, Cornell University, Ithaca, United StatesCenter for Genomics and Computational Biology, Department of Biomedical Engineering, Duke University, Durham, United States; Department of Biological and Environmental Engineering, Cornell University, Ithaca, United StatesDepartment of Pediatrics, Baylor College of Medicine, Houston, United StatesDepartment of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, United StatesDepartment of Pediatrics, Baylor College of Medicine, Houston, United StatesDepartment of Molecular Genetics, Ohio State University, Columbus, United StatesCenter for Genomics and Computational Biology, Department of Biomedical Engineering, Duke University, Durham, United States; Mienig School of Biomedical Engineering, Cornell University, Ithaca, United States; School of Electrical and Computer Engineering, Cornell University, Ithaca, United StatesNotch 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.https://elifesciences.org/articles/35710FringeGlycosylationNotch SignallingIntestinal CryptsLgr5+ Stem Cell |
| spellingShingle | 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 Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis eLife Fringe Glycosylation Notch Signalling Intestinal Crypts Lgr5+ Stem Cell |
| title | Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| title_full | Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| title_fullStr | Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| title_full_unstemmed | Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| title_short | Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| title_sort | radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis |
| topic | Fringe Glycosylation Notch Signalling Intestinal Crypts Lgr5+ Stem Cell |
| url | https://elifesciences.org/articles/35710 |
| work_keys_str_mv | AT preetishkadurlakshminarasimhamurthy radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT tarasrinivasan radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT matthewsbochter radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT ruixi radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT anastasiakristinevaranko radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT kueilingtung radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT fatihsemerci radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT kelixu radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT mirjanamaleticsavatic radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT susanecole radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis AT xilingshen radicalandlunaticfringesmodulatenotchligandstosupportmammalianintestinalhomeostasis |