Out on the Fringe: Modulation of Notch Signaling by Glycosylation

  • Keli XuEmail author
  • Sean E. EganEmail author


Differential glycosylation of Notch, often as part of a feedback loop, represents a powerful mechanism by which signaling is regulated. Together with Dll (Delta) and Jagged (Serrate) ligands, Fringe, Rumi, and other sugar transferase proteins form a remarkably versatile system to coordinate Notch-dependent tissue patterning. When Fringe is induced in the same cell as Dll, it enhances signal reception through Notch, downregulates Dll through cis-inhibition, and helps to make neighboring cells distinct. When induced in a Jagged-expressing cell, it helps to create a hybrid signal sender/receiver identity with low levels of Notch signal reception, accompanied by (Jagged) signal sending activity without cis-inhibition. In this situation, Fringe can help drive neighbors to the same state. Fringe can even work together with Dll3 to inhibit Notch signaling in neighboring cells. A detailed mechanism by which Fringes control development of several tissues has begun to emerge. With time, studies on Notch glycosylation should help define how this system is used to control development in most tissues and how it can be exploited for therapeutic benefit in the fight against cancer and cardiovascular disease.


Notch Lunatic Fringe Manic Fringe Radical Fringe Rumi Delta Serrate Dll Jagged Somitogenesis Lymphocyte development T-cells Human cancer 



K.X. is supported by grants from the National Institutes of Health. S.E.E. is supported by grants from the Terry Fox Foundation, the Canadian Breast Cancer Foundation, the Canadian Institutes for Health Research, and the Cancer Research Society. We thank Dr. Cynthia Guidos for valuable comments on the hematopoiesis and lymphocyte development section of the manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cancer Institute and Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical CenterJacksonUSA
  2. 2.Program in Cell Biology, The Hospital for Sick Children and Department of Molecular Genetics, University of TorontoTorontoCanada

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