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Gene Review

fng  -  fringe

Drosophila melanogaster

Synonyms: CG10580, D-Fng, D-fng, Dfng, Dmel\CG10580, ...
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Disease relevance of fng


High impact information on fng

  • Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis [2].
  • Glycosyltransferase activity of Fringe modulates Notch-Delta interactions [3].
  • The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that is likely to be relevant to other signalling pathways [4].
  • The Iroquois genes are expressed in the dorsal half of the eye and here we show that they regulate the expression of the secreted molecule Fringe [5].
  • Our results indicate that the formation of the Fringe boundary and subsequent Notch signalling at the equator are essential for organizing mirror symmetry and eye morphogenesis [6].

Biological context of fng

  • The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and glia, and is required for subtype-specific glial gene expression [7].
  • In ap mutants, the wing is lost [5] [9], and here we report that this phenotype can be rescued by ectopic expression of either Ser or fng and that, surprisingly, the resulting wings have both dorsal and ventral cell fates [8].
  • Our results indicate that glycosylation of an EGF domain proposed to be essential for ligand binding, EGF12, is crucial to the inhibition of Serrate-to-Notch signaling by Fringe [9].
  • Ectopic expression of lunatic Fringe leads to downregulation of Serrate-1 in the developing chick neural tube; analysis using in ovo electroporation transfection technique [10].
  • This has been confirmed by re-examination of fng mutants and analysis of fng mutant clones in oogenesis [11].

Anatomical context of fng

  • RESULTS: We report that a functional epitope-tagged form of Drosophila Fringe was localised in the Golgi apparatus [12].
  • We find that Fringe does not detectably affect the ligand-receptor interactions of the Notch pathway in cultured cells [13].
  • Ectopic Fringe borders that are generated by clones of fringe cells can reverse the planar polarity of photoreceptor clusters, indicating that the Fringe boundary is crucial for the induction of mirror symmetry [6].
  • In Drosophila, Fringe has been shown to play a role in modulating Notch-Delta signalling [3,4], a pathway which in vertebrates has been implicated in defining somite boundaries [5-9] [14].
  • Therefore, Manic, Lunatic, and Radical Fringe by modulating the Notch pathway may play a key role in defining the different steps of keratinocyte differentiation [15].

Associations of fng with chemical compounds

  • Further, we show that neurotic is required for Fringe activity, which encodes a fucose-specific beta1, 3 N-acetylglucosaminyltransferase, previously shown to modulate Notch receptor activity [16].
  • We show that Fringe specifically binds the nucleoside diphosphate UDP, a feature of many glycosyltransferases [12].
  • This expression decreases by a few days postnatally and can be reactivated by retinoic acid treatment, which triggers a new distribution of Fringe transcripts and a thickening of the granular layer [15].

Regulatory relationships of fng

  • However, activation of Notch does not itself confer either dorsal or ventral cell location, and fng can influence compartmentalization even within regions of ubiquitous Notch activation [17].

Other interactions of fng

  • We found that Ser and Dl maintain each other's expression by a positive feedback loop. fng is expressed specifically by dorsal cells and functions to position and restrict this feedback loop to the developing dorsal-ventral boundary [18].
  • One mechanism of crossboundary signaling is controlled by the Notch (N)-modifying protein Fringe (Fng) [19].
  • Here we report the results of experiments aimed at establishing the relationships between Fringe, Serrate and Delta during wing development [20].
  • Two glycosyltransferases that transfer sugars to EGF domains, OFUT1 and Fringe, regulate Notch signaling [9].
  • Here we show that fng has a dynamic expression pattern in oogenesis and that its expression in specific groups of follicle cells along the anterior-posterior and dorsal-ventral axes is defined by the repression of fng by Grk [11].


  1. Planar polarization of the denticle field in the Drosophila embryo: Roles for Myosin II (Zipper) and Fringe. Walters, J.W., Dilks, S.A., Dinardo, S. Dev. Biol. (2006) [Pubmed]
  2. The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through notch activation. Jordan, K.C., Clegg, N.J., Blasi, J.A., Morimoto, A.M., Sen, J., Stein, D., McNeill, H., Deng, W.M., Tworoger, M., Ruohola-Baker, H. Nat. Genet. (2000) [Pubmed]
  3. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Brückner, K., Perez, L., Clausen, H., Cohen, S. Nature (2000) [Pubmed]
  4. Fringe is a glycosyltransferase that modifies Notch. Moloney, D.J., Panin, V.M., Johnston, S.H., Chen, J., Shao, L., Wilson, R., Wang, Y., Stanley, P., Irvine, K.D., Haltiwanger, R.S., Vogt, T.F. Nature (2000) [Pubmed]
  5. A dorsal/ventral boundary established by Notch controls growth and polarity in the Drosophila eye. Domínguez, M., de Celis, J.F. Nature (1998) [Pubmed]
  6. Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye. Cho, K.O., Choi, K.W. Nature (1998) [Pubmed]
  7. The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and glia, and is required for subtype-specific glial gene expression. Thomas, G.B., van Meyel, D.J. Development (2007) [Pubmed]
  8. Wing development and specification of dorsal cell fates in the absence of apterous in Drosophila. Klein, T., Couso, J.P., Martinez Arias, A. Curr. Biol. (1998) [Pubmed]
  9. An O-fucose site in the ligand binding domain inhibits Notch activation. Lei, L., Xu, A., Panin, V.M., Irvine, K.D. Development (2003) [Pubmed]
  10. Ectopic expression of lunatic Fringe leads to downregulation of Serrate-1 in the developing chick neural tube; analysis using in ovo electroporation transfection technique. Sakamoto, K., Nakamura, H., Takagi, M., Takeda, S., Katsube, K. FEBS Lett. (1998) [Pubmed]
  11. Expression of fringe is down regulated by Gurken/Epidermal Growth Factor Receptor signalling and is required for the morphogenesis of ovarian follicle cells. Zhao, D., Clyde, D., Bownes, M. J. Cell. Sci. (2000) [Pubmed]
  12. The notch signalling regulator fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. Munro, S., Freeman, M. Curr. Biol. (2000) [Pubmed]
  13. Ligand-receptor interactions and trans-endocytosis of Delta, Serrate and Notch: members of the Notch signalling pathway in Drosophila. Klueg, K.M., Muskavitch, M.A. J. Cell. Sci. (1999) [Pubmed]
  14. The lunatic fringe gene is a target of the molecular clock linked to somite segmentation in avian embryos. McGrew, M.J., Dale, J.K., Fraboulet, S., Pourquié, O. Curr. Biol. (1998) [Pubmed]
  15. Differential expression pattern of the three Fringe genes is associated with epidermal differentiation. Thélu, J., Viallet, J.P., Dhouailly, D. J. Invest. Dermatol. (1998) [Pubmed]
  16. neurotic, a novel maternal neurogenic gene, encodes an O-fucosyltransferase that is essential for Notch-Delta interactions. Sasamura, T., Sasaki, N., Miyashita, F., Nakao, S., Ishikawa, H.O., Ito, M., Kitagawa, M., Harigaya, K., Spana, E., Bilder, D., Perrimon, N., Matsuno, K. Development (2003) [Pubmed]
  17. Fringe-dependent separation of dorsal and ventral cells in the Drosophila wing. Rauskolb, C., Correia, T., Irvine, K.D. Nature (1999) [Pubmed]
  18. Fringe modulates Notch-ligand interactions. Panin, V.M., Papayannopoulos, V., Wilson, R., Irvine, K.D. Nature (1997) [Pubmed]
  19. Dorsal-ventral midline signaling in the developing Drosophila eye. Sato, A., Tomlinson, A. Development (2007) [Pubmed]
  20. Interactions among Delta, Serrate and Fringe modulate Notch activity during Drosophila wing development. Klein, T., Arias, A.M. Development (1998) [Pubmed]
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