Lunatic Fringe Screensaver Games

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It is 1811, and Loony Lunatic is just a young boy, exploring the wilderness of Bulgaria. This is the tale of his first adventure, a trip to a little known land called Halloween Hill, where he learns of a great evil and with his trusty slingshot, sets. Lunatic Fringe was a Maelstrom-like game built-in to After Dark, a screen saver utility for Mac and Windows popular in the early- to mid-90s. Fringe Player, from Sealie Software, is a app that.

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LFNG
Identifiers
AliasesLFNG, SCDO3, LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
External IDs
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7p22.3Start2,512,529 bp[1]
End2,529,177 bp[1]
Gene location (Mouse)
Chr.Chromosome 5 (mouse)[2]
Band5 G2 5 79.15 cMStart140,607,320 bp[2]
End140,615,545 bp[2]
RNA expression pattern
More reference expression data
Gene ontology
Molecular function•transferase activity
•transferase activity, transferring glycosyl groups
•metal ion binding
•O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity
•molecular function
•acetylglucosaminyltransferase activity
Cellular component•extracellular vesicle
•integral component of membrane
•integral component of Golgi membrane
•Golgi apparatus
•membrane
•Golgi membrane
•extracellular region
Biological process•somitogenesis
•pattern specification process
•regulation of somitogenesis
•marginal zone B cell differentiation
•negative regulation of Notch signaling pathway involved in somitogenesis
•multicellular organism development
•T cell differentiation
•compartment pattern specification
•animal organ morphogenesis
•ovarian follicle development
•positive regulation of protein binding
•regulation of Notch signaling pathway
•positive regulation of Notch signaling pathway
•positive regulation of meiotic cell cycle
•protein O-linked fucosylation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002304
NM_001040167
NM_001040168
NM_001166355

RefSeq (protein)

NP_001035257
NP_001035258
NP_001159827
NP_002295

Location (UCSC)Chr 7: 2.51 – 2.53 MbChr 5: 140.61 – 140.62 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase, also known as LFNG and Lunatic Fringe,[5][6] is a human gene.[7]

This gene encodes a member of the glycosyltransferase superfamily. The encoded protein is a single-pass type II Golgi membrane protein that functions as a fucose-specific glycosyltransferase, adding an N-acetylglucosamine to the fucose residue of a group of signaling receptors involved in regulating cell fate decisions during development. Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. Alternatively spliced transcript variants that encode different isoforms have been described, however, not all variants have been fully characterized.[7]

Function[edit]

Lunatic Fringe (Lfng) is a gene whose role in embryonic development is to establish the anterior boundary of somites, which will eventually develop in vertebrae, ribs, and dermis.[8] Lunatic Fringe responds to certain threshold ratios of retinoic acid and FGF-8 in order to mark the anterior boundary of somites while another transcription factor, Hairy, responds to different threshold ratios of retinoic acid and FGF-8 to form the posterior boundaries of somites.[9]

Clinical significance[edit]

A defect associated with Lfng mutations is spondylocostal dysostosis. Spondylocostal dysostosis is characterized by segmentation problems in the developing vertebrae resulting in fusion or lack of vertebrae along with abnormalities in the ribs.[10] Clinically, spondylocostal dysostosis presents as a shortened neck and trunk relative total height and a mild form of scoliosis. Respiratory problems are also common in spondylocostal dysostosis because of the shortened trunk.

A knockout model for Lfng has been created in mice, and without Lfng, mice have shorter tails, and impaired rib, lung, and somite development. A deficiency of Lfng in male mice has also been associated with lack of spermatozoa in the epididymis of many mice; however, spermatogenesis was not impaired. Rather, the male mice were subfertile.[11] In female mice, Lfng deficiency led to infertility because of abnormal folliculogenesis. Further examination showed that oocytes from these female mice did not complete meiotic maturation.[12] However, there are other studies that contradict this stating that not all female mile deficient of Lfng are infertile. A possible explanation for this difference between these studies is that the Lfng alleles were functional different, however, this is unlikely. More likely is that this discrepancy results from differences in the genetic background of the mice or husbandry and colony conditions.[13]

Impact of mutation[edit]

Lunatic Fringe is a transcription factor that plays a crucial role in the development of the somites. Somites give rise to the skeletal muscle, the axial skeleton, the tendons, and the dorsal dermis. The somites are formed via the clock-wave front model, and as each somite is formed, each cell receives a burst of FGF8 (a signaling molecule). Somites are formed anterior to posterior, and since FGF8 has a short half-life, this leads to a greater concentration of FGF8 in the posterior, and a lesser concentration in the anterior. Lunatic fringe responds to the lower concentration of FGF8 in the anterior and leads these cells to their developmental fate. Mutation of the Lunatic Fringe gene can cause severe Spondylocostal Dysostosis, which involves vertebral segmentation defects and rib abnormalities. A mutation was discovered in which a conservative phenylalanine close to the active site of the enzyme mutates, leading to the enzymatic inactivation of Lunatic Fringe. A “knock-out” model has been created using mice. In mice, Lunatic Fringe plays a crucial role in the Notch signaling pathway during the formation of somites, and a mutation in this gene leads to somites with irregular shapes and a defect in the anterior-posterior formation.

References[edit]

  1. ^ abcGRCh38: Ensembl release 89: ENSG00000106003 - Ensembl, May 2017
  2. ^ abcGRCm38: Ensembl release 89: ENSMUSG00000029570 - Ensembl, May 2017
  3. ^'Human PubMed Reference:'. National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^'Mouse PubMed Reference:'. National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Egan S, Herbrick JA, Tsui LC, Cohen B, Flock G, Beatty B, Scherer SW (December 1998). 'Mapping of the human Lunatic Fringe (LFNG) gene to 7p22 and Manic Fringe (MFNG) to 22q12'. Genomics. 54 (3): 576–7. doi:10.1006/geno.1998.5559. PMID9878264.
  6. ^'Troublesome gene names get the boot', 6 November 2006, Michael Hopkin, nature.com
  7. ^ ab'Entrez Gene: LFNG LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase'.
  8. ^Serth K, Schuster-Gossler K, Cordes R, Gossler A (April 2003). 'Transcriptional oscillation of lunatic fringe is essential for somitogenesis'. Genes & Development. 17 (7): 912–25. doi:10.1101/gad.250603. PMC196028. PMID12670869.
  9. ^Shifley ET, Vanhorn KM, Perez-Balaguer A, Franklin JD, Weinstein M, Cole SE (March 2008). 'Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton'. Development. 135 (5): 899–908. doi:10.1242/dev.006742. PMID18234727.
  10. ^ abSparrow DB, Chapman G, Wouters MA, Whittock NV, Ellard S, Fatkin D, Turnpenny PD, Kusumi K, Sillence D, Dunwoodie SL (January 2006). 'Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype'. American Journal of Human Genetics. 78 (1): 28–37. doi:10.1086/498879. PMC1380221. PMID16385447.
  11. ^Hahn KL, Beres B, Rowton MJ, Skinner MK, Chang Y, Rawls A, Wilson-Rawls J (January 2009). 'A deficiency of lunatic fringe is associated with cystic dilation of the rete testis'. Reproduction. 137 (1): 79–93. doi:10.1530/REP-08-0207. PMC5739036. PMID18801836.
  12. ^Hahn KL, Johnson J, Beres BJ, Howard S, Wilson-Rawls J (February 2005). 'Lunatic fringe null female mice are infertile due to defects in meiotic maturation'. Development. 132 (4): 817–28. doi:10.1242/dev.01601. PMID15659488.
  13. ^Xu J, Norton CR, Gridley T (February 2006). 'Not all lunatic fringe null female mice are infertile'. Development. 133 (4): 579, author reply 579–80. doi:10.1242/dev.02221. PMID16436621.
  14. ^Zhang N, Gridley T (July 1998). 'Defects in somite formation in lunatic fringe-deficient mice'. Nature. 394 (6691): 374–7. doi:10.1038/28625. PMID9690472.

Further reading[edit]

  • Johnston SH, Rauskolb C, Wilson R, Prabhakaran B, Irvine KD, Vogt TF (June 1997). 'A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway'. Development. 124 (11): 2245–54. PMID9187150.
  • Moran JL, Johnston SH, Rauskolb C, Bhalerao J, Bowcock AM, Vogt TF (June 1999). 'Genomic structure, mapping, and expression analysis of the mammalian Lunatic, Manic, and Radical fringe genes'. Mammalian Genome. 10 (6): 535–41. doi:10.1007/s003359901039. PMID10341080.
  • Moloney DJ, Panin VM, Johnston SH, Chen J, Shao L, Wilson R, Wang Y, Stanley P, Irvine KD, Haltiwanger RS, Vogt TF (July 2000). 'Fringe is a glycosyltransferase that modifies Notch'. Nature. 406 (6794): 369–75. doi:10.1038/35019000. PMID10935626.
  • Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (July 2001). 'Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation'. The Journal of Biological Chemistry. 276 (28): 25753–8. doi:10.1074/jbc.M103473200. PMID11346656.
  • Cole SE, Levorse JM, Tilghman SM, Vogt TF (July 2002). 'Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis'. Developmental Cell. 3 (1): 75–84. doi:10.1016/S1534-5807(02)00212-5. PMID12110169.
  • Shao L, Moloney DJ, Haltiwanger R (March 2003). 'Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region'. The Journal of Biological Chemistry. 278 (10): 7775–82. doi:10.1074/jbc.M212221200. PMID12486116.
  • Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (December 2005). 'Transcriptome analysis of human gastric cancer'. Mammalian Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID16341674.
  • Sparrow DB, Chapman G, Wouters MA, Whittock NV, Ellard S, Fatkin D, Turnpenny PD, Kusumi K, Sillence D, Dunwoodie SL (January 2006). 'Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype'. American Journal of Human Genetics. 78 (1): 28–37. doi:10.1086/498879. PMC1380221. PMID16385447.

External links[edit]

Retrieved from 'https://en.wikipedia.org/w/index.php?title=LFNG&oldid=883098598'