Gene Symbol: Nf1
Description: Neurofibromin 1
Alias: CG8318, Dmel\CG8318, FBpp0084326, NF-1, NF1, Nf-1, dNF1, dNf1, nf1, neurofibromin 1, CG8318-PB, CG8318-PC, CG8318-PD, CG8318-PE, CG8318-PF, Neurofibromatosis-1, Nf1-PB, Nf1-PC, Nf1-PD, Nf1-PE, Nf1-PF, neurofibramatosis-1, neurofibromatosis 1, neurofibromatosis factor 1, neurofibromatosis type 1, neurofibromin
Species: fruit fly

Top Publications

  1. The I, Hannigan G, Cowley G, Reginald S, Zhong Y, Gusella J, et al. Rescue of a Drosophila NF1 mutant phenotype by protein kinase A. Science. 1997;276:791-4 pubmed
    The neurofibromatosis type 1 (NF1) tumor suppressor protein is thought to restrict cell proliferation by functioning as a Ras-specific guanosine triphosphatase-activating protein...
  2. Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y. Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci. 2002;5:95-6 pubmed
    b>Neurofibromatosis type 1 (NF1) is a dominant genetic disorder characterized by multiple benign and malignant nervous system tumors, and by learning defects in 45% of children with NF1 mutations...
  3. Guo H, Tong J, Hannan F, Luo L, Zhong Y. A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature. 2000;403:895-8 pubmed
    The tumour-suppressor gene Neurofibromatosis 1 (Nf1) encodes a Ras-specific GTPase activating protein (Ras-GAP)...
  4. Gouzi J, Moressis A, Walker J, Apostolopoulou A, Palmer R, Bernards A, et al. The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila growth and learning. PLoS Genet. 2011;7:e1002281 pubmed publisher
    ..of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene...
  5. Guo H, The I, Hannan F, Bernards A, Zhong Y. Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science. 1997;276:795-8 pubmed
    The human neurofibromatosis type 1 (NF1) tumor suppressor protein functions as a Ras-specific guanosine triphosphatase-activating protein, but the identity of Ras- mediated pathways modulated by NF1 remains unknown...
  6. Hannan F, Ho I, Tong J, Zhu Y, Nurnberg P, Zhong Y. Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. Hum Mol Genet. 2006;15:1087-98 pubmed the Drosophila brain, which is disrupted by mutations in the epidermal growth factor receptor (EGFR), neurofibromin (NF1) and Ras, but not Galpha(s)...
  7. Walker J, Tchoudakova A, McKenney P, Brill S, Wu D, Cowley G, et al. Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. Genes Dev. 2006;20:3311-23 pubmed
    b>Neurofibromatosis type 1 (NF1) is among the most common genetic disorders of humans and is caused by loss of neurofibromin, a large and highly conserved protein whose only known function is to serve as a GTPase-Activating Protein (GAP) ..
  8. Tong J, Schriner S, McCleary D, Day B, Wallace D. Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster. Nat Genet. 2007;39:476-85 pubmed
    ..Thus, neurofibromin regulates longevity and stress resistance through cAMP regulation of mitochondrial respiration and ROS ..
  9. Buchanan M, Davis R. A distinct set of Drosophila brain neurons required for neurofibromatosis type 1-dependent learning and memory. J Neurosci. 2010;30:10135-43 pubmed publisher
    Nonspecific cognitive impairments are one of the many manifestations of neurofibromatosis type 1 (NF1). A learning phenotype is also present in Drosophila melanogaster that lack a functional neurofibromin gene (nf1)...

More Information


  1. Oldham S, Bohni R, Stocker H, Brogiolo W, Hafen E. Genetic control of size in Drosophila. Philos Trans R Soc Lond B Biol Sci. 2000;355:945-52 pubmed
    ..In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin-like growth factor-I and other growth pathways in the control of cell, organ and body size. ..
  2. Hong S, Bang S, Hyun S, Kang J, Jeong K, Paik D, et al. cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila. Nature. 2008;454:771-5 pubmed publisher
    ..Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants...
  3. Reis M, Páscoa I, Rocha H, Aguiar B, Vieira C, Vieira J. Genes belonging to the insulin and ecdysone signaling pathways can contribute to developmental time, lifespan and abdominal size variation in Drosophila americana. PLoS ONE. 2014;9:e86690 pubmed publisher
    ..americana, pleiotropic genes involved in the highly-conserved insulin and ecdysone signaling pathways are likely responsible for variation observed in ecologically relevant phenotypic traits, although other genes are also involved. ..
  4. Tsai P, Wang M, Kao H, Cheng Y, Walker J, Chen R, et al. Neurofibromin mediates FAK signaling in confining synapse growth at Drosophila neuromuscular junctions. J Neurosci. 2012;32:16971-81 pubmed publisher
    ..Although downstream pathways are well studied, regulation of the NF1-encoded neurofibromin protein is less clear...
  5. Burrell B, Sahley C. Learning in simple systems. Curr Opin Neurobiol. 2001;11:757-64 pubmed
    ..Some pathways contribute to a single stage of memory formation, whereas others impact on multiple stages of memory development. Distinct cellular pathways may also act in series or in parallel during various stages of memory formation. ..
  6. Holmes T, Sheeba V. Circadian pathway: the other shoe drops. Curr Biol. 2005;15:R987-9 pubmed
    ..The discovery of the PDF receptor heralds progress in understanding the circadian pacemaker circuit and output pathways in insects. ..
  7. Lee S, Eyre Walker Y, Rane R, Reuter C, Vinti G, Rako L, et al. Polymorphism in the neurofibromin gene, Nf1, is associated with antagonistic selection on wing size and development time in Drosophila melanogaster. Mol Ecol. 2013;22:2716-25 pubmed publisher
    ..We consider variation in the CNS-specific gene neurofibromin 1 (Nf1) and its association with body size and development time...
  8. King L, Koch M, Murphy K, Velazquez Y, Ja W, Tomchik S. Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila. G3 (Bethesda). 2016;6:1083-93 pubmed publisher
    ..The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans...
  9. Stanewsky R. Clock mechanisms in Drosophila. Cell Tissue Res. 2002;309:11-26 pubmed
    ..Although their regulation depends on the major clock genes, the majority of the clock-controlled genes are not direct targets of clock factors. ..
  10. Kwon H, Kim S, Kim S, Jang I, Ahn Y, Lee W, et al. Drosophila extracellular signal-regulated kinase involves the insulin-mediated proliferation of Schneider cells. J Biol Chem. 2002;277:14853-8 pubmed
    ..The depletion of DERK or DMKP-3 by inhibitory double-stranded RNA decreased and increased BrdU incorporation, respectively. Thus, we propose that DERK is involved in the proliferation of Schneider cells via the insulin pathway. ..
  11. Ma L, Ma J, Xu K. Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster. PLoS ONE. 2015;10:e0121600 pubmed publisher
  12. Hashimoto H, Shintani N, Baba A. Higher brain functions of PACAP and a homologous Drosophila memory gene amnesiac: insights from knockouts and mutants. Biochem Biophys Res Commun. 2002;297:427-31 pubmed
    ..A functional comparison between PACAP and amnesiac underlines phylogenetically conserved functions across phyla and may provide insights into the possible mechanisms of action and evolution of this neuropeptidergic system. ..
  13. Yager J, Richards S, Hekmat Scafe D, Hurd D, Sundaresan V, Caprette D, et al. Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways. Proc Natl Acad Sci U S A. 2001;98:10445-50 pubmed
    ..amn, which encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide; and NF1, the Drosophila ortholog of the human gene responsible for type 1 neurofibromatosis...
  14. van Dam T, Bos J, Snel B. Evolution of the Ras-like small GTPases and their regulators. Small Gtpases. 2011;2:4-16 pubmed
    ..Altogether, our analysis forms an extensive evolutionary framework for Ras-like signaling pathways and provides specific predictions for molecular biologists and biochemists. ..
  15. Bonneau F, D Angelo I, Welti S, Stier G, Ylanne J, Scheffzek K. Expression, purification and preliminary crystallographic characterization of a novel segment from the neurofibromatosis type 1 protein. Acta Crystallogr D Biol Crystallogr. 2004;60:2364-7 pubmed
    Neurofibromin (MW 320 kDa) is the protein responsible for the pathogenesis of neurofibromatosis type 1 (NF1), one of the most common genetic diseases worldwide...
  16. Davis R. Neurofibromin progress on the fly. Nature. 2000;403:846-7 pubmed
  17. Cooper M, Tyler D, Furriols M, Chalkiadaki A, Delidakis C, Bray S. Spatially restricted factors cooperate with notch in the regulation of Enhancer of split genes. Dev Biol. 2000;221:390-403 pubmed
  18. Roman G, Davis R. Molecular biology and anatomy of Drosophila olfactory associative learning. Bioessays. 2001;23:571-81 pubmed
    ..In this review, we discuss the nature of the behavioral tasks, the molecules, and the neuronal circuits involved in olfactory learning in Drosophila. ..
  19. Liu X, Buchanan M, Han K, Davis R. The GABAA receptor RDL suppresses the conditioned stimulus pathway for olfactory learning. J Neurosci. 2009;29:1573-9 pubmed publisher enhance learning in animals carrying mutations in genes of the cAMP signaling pathway, such as rutabaga and NF1, suggesting that RDL works up stream of these functions in CS/US integration...
  20. Hendricks J. Invited review: Sleeping flies don't lie: the use of Drosophila melanogaster to study sleep and circadian rhythms. J Appl Physiol (1985). 2003;94:1660-72; discussion 1673 pubmed
    ..Nonetheless, studies have already established that two transcription factors alter rest and rest homeostasis. The implications of these advances for the future of sleep research are summarized. ..
  21. Ho I, Hannan F, Guo H, Hakker I, Zhong Y. Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation. J Neurosci. 2007;27:6852-7 pubmed
    b>Neurofibromatosis type 1 (NF1) is a dominant genetic disorder that causes tumors of the peripheral nervous system. In addition, >40% of afflicted children have learning difficulties...
  22. Walker J, Bernards A. A Drosophila screen identifies neurofibromatosis-1 genetic modifiers involved in systemic and synaptic growth. Rare Dis. 2014;2:e28341 pubmed publisher
    b>Neurofibromatosis type 1 (NF1) is caused by loss of a negative regulator of Ras oncoproteins. Unknown genetic modifiers have been implicated in NF1's characteristic variability...
  23. Cooper M, Bray S. Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature. 1999;397:526-30 pubmed
  24. Li W, Cressy M, Qin H, Fulga T, Van Vactor D, Dubnau J. MicroRNA-276a functions in ellipsoid body and mushroom body neurons for naive and conditioned olfactory avoidance in Drosophila. J Neurosci. 2013;33:5821-33 pubmed publisher
    ..The dual role of this miR-276a::DopR genetic module in these two neural circuits highlights the importance of miRNA-mediated gene regulation within distinct circuits underlying both naive behavioral responses and memory...
  25. Houot B, Fraichard S, Greenspan R, Ferveur J. Genes involved in sex pheromone discrimination in Drosophila melanogaster and their background-dependent effect. PLoS ONE. 2012;7:e30799 pubmed publisher
  26. Davis R. Mushroom bodies, Ca(2+) oscillations, and the memory gene amnesiac. Neuron. 2001;30:653-6 pubmed
    ..Slow and spontaneous oscillations of calcium levels are elevated in the mushroom body neurons of amnesiac mutants and may contribute to memory consolidation. ..
  27. Williams J, Su H, Bernards A, Field J, Sehgal A. A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK. Science. 2001;293:2251-6 pubmed
    ..In Drosophila, null mutations of the neurofibromatosis-1 (Nf1) gene produce abnormalities of circadian rhythms in locomotor activity...
  28. Mertens I, Vandingenen A, Johnson E, Shafer O, Li W, Trigg J, et al. PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. Neuron. 2005;48:213-9 pubmed
    ..As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase...
  29. Zars T. Behavioral functions of the insect mushroom bodies. Curr Opin Neurobiol. 2000;10:790-5 pubmed
    ..In addition, the mushroom bodies are necessary for context generalization in visual learning and for regulating the transition from walking to rest. ..
  30. Stocker H, Hafen E. Genetic control of cell size. Curr Opin Genet Dev. 2000;10:529-35 pubmed
    ..Evidence is emerging for a signalling cascade conserved in evolution that links external nutrient sources to cell size. ..
  31. Kumar J, Hsiung F, Powers M, Moses K. Nuclear translocation of activated MAP kinase is developmentally regulated in the developing Drosophila eye. Development. 2003;130:3703-14 pubmed
    ..We also show that MAPK cytoplasmic hold has an essential function in vivo: if it is overcome, developmental patterning in the furrow is disrupted. ..
  32. van der Voet M, Harich B, Franke B, Schenck A. ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila. Mol Psychiatry. 2016;21:565-73 pubmed publisher
    ..DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1)...
  33. Jindal G, Goyal Y, Burdine R, Rauen K, Shvartsman S. RASopathies: unraveling mechanisms with animal models. Dis Model Mech. 2015;8:769-82 pubmed publisher
    ..Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment. ..
  34. Bergmann A, Tugentman M, Shilo B, Steller H. Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling. Dev Cell. 2002;2:159-70 pubmed
    ..Therefore, a direct pathway linking a specific extracellular survival factor with a caspase-based death program has been established. ..
  35. Wurmbach E, Preiss A. Deletion mapping in the Enhancer of split complex. Hereditas. 2014;151:159-68 pubmed publisher
    ..Larger deletions, generated also by X-ray mutagenesis, uncover most of the E(spl)-C. The phenotypes of homozygous deficient embryos were analysed to characterize the respective loss of Notch signalling activity. ..
  36. Stanewsky R. Genetic analysis of the circadian system in Drosophila melanogaster and mammals. J Neurobiol. 2003;54:111-47 pubmed
    ..This review will try to give a comparative overview about the two systems, highlighting similarities as well as specifics of both insect and murine clocks. ..
  37. Adewoye A, Kyriacou C, Tauber E. Identification and functional analysis of early gene expression induced by circadian light-resetting in Drosophila. BMC Genomics. 2015;16:570 pubmed publisher
    ..continuous light normally causes arrhythmicity in wild-type flies, the knockdown of Kr-h1, Nipped-A, Thor, nrv1, Nf1, CG11155 (ionotropic glutamate receptor), and Fmr1 resulted in flies that were rhythmic, suggesting a disruption in ..
  38. Bai L, Sehgal A. Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep. PLoS Genet. 2015;11:e1005611 pubmed publisher
    ..In particular, Alk genetically interacts with Neurofibromatosis 1 (Nf1) to regulate growth and associative learning in flies. We show that Alk mutants have increased sleep...
  39. Morley K, Montgomery G. The genetics of cognitive processes: candidate genes in humans and animals. Behav Genet. 2001;31:511-31 pubmed
    ..This survey confirms that many genes are associated with cognitive variation and highlights the potential importance of animal models in the study of human cognition. ..