Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila

Cohen, Brenda; Bashirullah, Arash; Dagnino, Lina; Campbell, Christine; Fisher, William W.; Leow, Ching Ching; Whiting, Elisabeth; Ryan, David K.; Zinyk, Dawn; Boulianne, Gabrielle L.; Hui, Chi‐chung; Gallie, Brenda L.; Phillips, Robert A.; Lipshitz, Howard D.; Egan, Sean E.

doi:10.1038/ng0797-283

Cited by 142 publications

(97 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In some tissues where the expression pattern has been documented in detail, e.g., nervous system (Cohen et al, 1997;Ishii et al, 2000), epidermis (Cohen et al, 1997;Thelu et al, 2002), teeth (Harada et al, 1999;Pouyet and Mitsiadis, 2000;Mustonen et al, 2002), and hair follicles (Favier et al, 2000;Chen and Chuong, 2000), fringe expression appears to mark a contrast between uncommitted cells, which express lunatic fringe, and their committed progeny, which express radical and/or manic fringe, but it is clear from our present data in the zebrafish that this is by no means a universal rule. Moreover, patterns of expression of fringe genes are not always conserved.…”

Section: Expression Patterns Of Fringe Genes In Different Vertebratescontrasting

confidence: 53%

“…1A for details, Wu et al, 1996;Johnston et al, 1997;Cohen et al, 1997;Laufer et al, 1997;Rodriguez-Esteban et al, 1997;Cadinouche et al, 1999;Mikami et al, 2001), including a putative signal peptide, potential N-linked glycosylation sites, a DXDmotif responsible for the glycosyltransferase catalytic activity (Moloney et al, 2000;Brü ckner et al, 2000) and six conserved cysteines that are thought to form disulfide bonds (Irvine and Wieschaus, 1994). Interestingly, the putative tetrabasic proteolytic sites are only found in Xenopus and chicken Rfng, suggesting that zebrafish, newt, rat, mouse, and human Rfng proteins may not require regulated proteolytic activation.…”

Section: Cloning and Sequence Analysismentioning

confidence: 99%

See 1 more Smart Citation

Sequence and embryonic expression of three zebrafish fringe genes: lunatic fringe, radical fringe, and manic fringe

Qiu

Haddon

et al. 2004

Developmental Dynamics

View full text Add to dashboard Cite

Drosophila fringe and its homologues in vertebrates code for glycosyltransferases that modify Notch, altering the sensitivity of this receptor protein to its ligands Delta and Serrate and, thereby, playing an essential part in the demarcation of tissue boundaries. We describe the isolation and characterization of three zebrafish (Danio rerio) fringe homologues: lunatic fringe (lfng), radical fringe (rfng), and manic fringe (mfng). In addition to the sites previously described (Prince et al.

show abstract

Section: Expression Patterns Of Fringe Genes In Different Vertebratescontrasting

confidence: 53%

Section: Cloning and Sequence Analysismentioning

confidence: 99%

Sequence and embryonic expression of three zebrafish fringe genes: lunatic fringe, radical fringe, and manic fringe

Qiu

Haddon

et al. 2004

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Multiple alignment provides a more stringent comparison than simple pairwise alignments, and these 84 amino acids constitute a core of structural elements that are presumably essential for normal FNG function. The high degree of sequence similarity among fng genes is consistent with the conserved enzymatic activity of Drosophila and mammalian FNG (8), and with the biological activity of mouse fng genes expressed in Drosophila (15,16).…”

Section: Resultsmentioning

confidence: 72%

Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila

Correia

Papayannopoulos

Panin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fringe proteins are ␤1,3-N-acetylglucosaminyltransferases that modulate signaling through Notch receptors by modifying Olinked fucose on epidermal growth factor domains. Fringe is highly conserved, and comparison among 18 different Fringe proteins from 11 different species identifies a core set of 84 amino acids that are identical among all Fringes. Fringe is only distantly related to other glycosyltransferases, but analysis of the predicted Drosophila proteome identifies a set of four sequence motifs shared among Fringe and other putative ␤1,3-glycosyltransferases. To gain functional insight into these conserved sequences, we genetically and molecularly characterized 14 point mutations in Drosophila fringe. Most nonsense mutations act as recessive antimorphs, raising the possibility that Fringe may function as a dimer. Missense mutations identify two distinct motifs that are conserved among ␤1,3-glycosyltransferases, and that can be modeled onto key motifs in the crystallographic structures of bovine ␤1,4-galactosyltransferase 1 and human glucuronyltransferase I. Other missense mutations map to amino acids that are conserved among Fringe proteins, but not among other glycosyltransferases, and thus may identify structural motifs that are required for unique aspects of Fringe activity. Although the Notch pathway mediates a wide range of cell fate decisions, the influence of fringe ( fng) genes on Notch signaling has been best studied during the development of the Drosophila wing. In the developing wing imaginal disk, FNG inhibits the ability of Serrate to activate Notch, and potentiates the ability of Delta to activate Notch. These effects of FNG position a stripe of Notch activation along the border between dorsal and ventral cells, which is essential for the subsequent patterning, growth, and compartmentalization of the wing (reviewed in refs. 5 and 6).Drosophila and vertebrate FNG proteins are highly conserved and possess an unusual ␤1,3-N-acetylglucosaminyltransferase activity that elongates O-linked fucose within EGF domains (7,8). Although FNG is not closely related to other glycosyltransferases, it does share a few short sequence motifs with certain other glycosyltransferases (9), and we report here that it is most closely related to members of a ␤1,3-glycosyltransferase (␤3GT) superfamily. These enzymes use a variety of sugar donors and acceptors, but all transfer the sugar from a UDP-sugar donor, creating a ␤ linkage between the 1 carbon of the donor and the 3 carbon of the acceptor. With the exception of site-directed mutations in a DDD motif of FNG (7,8,10,38), the functional requirements for conserved sequence motifs in FNG or other ␤3GTs have not been assessed. Moreover, the only crystallographic structure for a ␤3GT determined to date is that of human glucuronyltransferase I (GlcAT-I), which does not share significant primary sequence similarity with FNG.Here, we employ two complementary approaches to identify functionally important amino acids within FNG: sequence conservation, and genetic and mole...

show abstract

“…Embryos were stained with BM Purple AP substrate (Roche Molecular Biochemicals) and postfixed with 4% PFA in PBS. The following probes were used: Hand1 (eHAND) (Srivastava et al, 1995); Nodal (Zhou et al, 1993); Lefty1 (Ebaf) and Lefty2 (Leftb) (Meno et al, 1997); Pitx2 ; T (brachyury) (Herrmann, 1991); Hnf3b (Ang et al, 1993); Dll1 (Bettenhausen et al, 1995); Dll3 (Dunwoodie et al, 1997); Jag1 (Mitsiadis et al, 1997); Notch1 (Del Amo et al, 1992); Notch2 (Larsson et al, 1994); and Lfng (Cohen et al, 1997).…”

Section: Mice and Embryo Collectionmentioning

confidence: 99%

Node and midline defects are associated with left-right development inDelta1mutant embryos

Przemeck¹,

Heinzmann²,

Beckers³

et al. 2003

Development

View full text Add to dashboard Cite

Axes formation is a fundamental process of early embryonic development. In addition to the anteroposterior and dorsoventral axes, the determination of the left-right axis is crucial for the proper morphogenesis of internal organs and is evolutionarily conserved in vertebrates. Genes known to be required for the normal establishment and/or maintenance of left-right asymmetry in vertebrates include, for example, components of the TGF-β family of intercellular signalling molecules and genes required for node and midline function. We report that Notch signalling, which previously had not been implicated in this morphogenetic process, is required for normal left-right determination in mice. We show, that the loss-of-function of the delta 1 (Dll1) gene causes a situs ambiguous phenotype, including randomisation of the direction of heart looping and embryonic turning. The most probable cause for this left-right defect in Dll1 mutant embryos is a failure in the development of proper midline structures. These originate from the node, which is disrupted and deformed in Dll1 mutant embryos. Based on expression analysis in wild-type and mutant embryos, we suggest a model, in which Notch signalling is required for the proper differentiation of node cells and node morphology.

show abstract

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila

Cited by 142 publications

References 29 publications

Sequence and embryonic expression of three zebrafish fringe genes: lunatic fringe, radical fringe, and manic fringe

Sequence and embryonic expression of three zebrafish fringe genes: lunatic fringe, radical fringe, and manic fringe

Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila

Node and midline defects are associated with left-right development inDelta1mutant embryos

Contact Info

Product

Resources

About