Fringe modulates Notch–ligand interactions

Abstract

The Notch family of transmembrane receptor proteins mediate developmental cell-fate decisions, and mutations in mammalian Notch genes have been implicated in leukaemia, breast cancer, stroke and dementia. During wing development in Drosophila, the Notch receptor is activated along the border between dorsal and ventral cells, leading to the specification of specialized cells that express Wingless (Wg) and organize wing growth and patterning. Three genes, fringe (fng), Serrate (Ser) and Delta (Dl), are involved in the cellular interactions leading to Notch activation. Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein. We have investigated the relationship between these genes by a combination of expression and coexpression studies in the Drosophila wing. 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. This is achieved by fng through a cell-autonomous mechanism that inhibits a cell's ability to respond to Serrate protein and potentiates its ability to respond to Delta protein.

Lunatic fringe causes expansion and increased neurogenesis of trunk neural tube and neural crest populations

“…Because lunatic fringe has been proposed to potentiate Notch-Delta signaling (Panin et al, 1997;Moloney et al, 2000), we tested whether lunatic fringe over-expression altered the levels or distribution patterns of members of the Notch signaling pathway to better understand the mechanisms by which lunatic fringe might regulate trunk neural crest production. In particular, we examined the effects of excess lunatic fringe on Notch-1 and its ligand Delta-1.…”

Molecular Genetics of Vestibular Organ Development

“…L-fng is an ortholog of the Drosophila fringe gene that acts in the Notch signaling pathway to establish boundaries during the development of both flies and vertebrates (Laufer et al 1997;Panin et al 1997;Evrard et al 1998;Papayannopoulos et al 1998;Zhang and Gridley 1998). Recent data show that Fringe mediates its effect by forming complexes with Notch receptors and modulating their ligand preferences (Hicks et al 2000;Ju et al 2000).…”

Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells

“…Genetic studies in Drosophila have indicated the existence of Notch modifying genes such as numb and fringe. 34,35 For example, association of Fringe with Notch-1 impairs Serrate (Jagged)-mediated signaling, but is permissive for Delta-mediated signaling. 36 Mammalian homologues of these genes have been identified.…”