Genomic structure, mapping, and expression analysis of the mammalian Lunatic, Manic, and Radical fringe genes

The three members of the mammalian fringe gene family, Manic fringe (Mfng), Radical fringe (Rfng), and Lunatic fringe (Lfng), were identified on the b asis of their similarity to Drosophila fringe (fng) and their participation in the evolutionarily conserved Notch receptor signaling pathway. Fringe g enes encode pioneer secretory proteins with weak similarity to glycosyltran sferases. Both expression patterns and functional studies support an import ant role for Fringe genes in patterning during embryonic development and an association with cellular transformation. We have now further characterize d the expression and determined the chromosomal localization and genomic st ructure of the mouse Mfng, Rfng, and Lfng genes; the genomic structure and conceptual open reading frame of the human RFNG gene; and the refined chrom osomal localization of the three human fringe genes. The mouse Fringe genes are expressed in the embryo and in adult tissues. The mouse and human Frin ge family members map to three different chromosomes in regions of conserve d synteny: Mfng maps to mouse Chr 15, and MFNG maps to human Chr 22q13.1 in the region of two cancer-associated loci; Lfng maps to mouse Chr 5, and LN G maps to human Chr 7p22; Rfng maps to mouse Chr 11, and RFNG maps to human Chr 17q25 in the minimal region for a familial psoriasis susceptibility lo cus. Characterization of the ge nomic loci of the Fringe gene family member s reveals a conserved genomic organization of 8 exons. Comparative analysis of mammalian Fringe genomic organization suggests that the first exon is e volutionarily labile and that the Fringe genes have a genomic structure dis tinct from those of previously characterized glycosyltransferases.